Author: "Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris" - Searchworks@Jio Institute Digital Library Search Results

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Start Over Author "Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris"

250 results on '"Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris"'

1. Assessing the Extent of Potential Inversion by Cyclic Voltammetry: Theory, Pitfalls, and Application to a Nickel Complex with Redox-Active Iminosemiquinone Ligands

Author: Cheriehan Hessin, Jules Schleinitz, Nolwenn Le Breton, Sylvie Choua, Laurence Grimaud, Vincent Fourmond, Marine Desage-El Murr, Christophe Léger, Institut de Chimie de Strasbourg, Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Bioénergétique et Ingénierie des Protéines (BIP ), and Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Inorganic Chemistry, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Physical and Theoretical Chemistry, [CHIM.OTHE]Chemical Sciences/Other
Abstract: International audience; Potential inversion refers to the situation where a protein cofactor or a synthetic molecule can be oxidized or reduced twice in a cooperative manner, that is the second electron transfer (ET) is easier than the first. This property is very important regarding the catalytic mechanism of enzymes that bifurcate electrons and the properties of bidirectional redox molecular catalysts that function in either direction of the reaction with no overpotential. Cyclic voltammetry is the most common technique for characterizing the thermodynamics and kinetics of ET to or from these molecules. However, a gap in the literature is the absence of analytical predictions to help interpret the values of the voltammetric peak potentials when potential inversion occurs ; the cyclic voltammograms are therefore often analyzed by simulating the data, with no discussion of the possibility of overfitting and often no estimation of the error on the determined parameters. Here we formulate the theory for the voltammetry of freely-diffusing or surface-confined two-electron redox species in the experimentally relevant irreversible limit where the peak separation depends on scan rate. We explain why the model is intrinsically underdetermined, and we illustrate this conclusion by the analysis of the voltammetry of a Ni complex with redox-active iminosemiquinone ligands. Being able to characterize the thermodynamics of two-electron transfer reactions will be crucial for designing more efficient catalysts.
Published: 2023

2. Characterization through scanning electron microscopy and μFourier transform infrared spectroscopy of microcalcifications present in fine needle aspiration smears

Author: Henry, Lucas, Bazin, Dominique, Policar, Clotilde, Haymann, Jean-Philippe, Daudon, Michel, Frochot, Vincent, Mathonnet, Muriel, Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL), Sorbonne Université (SU), Université Paris-Saclay, Laboratoire de Physique des Solides (LPS), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Dupuytren [CHU Limoges], ENS-PSL (LH's PhD fellowship)Fondation pour la Recherche Biomédicale (project DEI20151234413), and Policar, Clotilde
Subjects: Thyroid, [CHIM.INOR] Chemical Sciences/Inorganic chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Microscopie électronique à balayage, Spectroscopie infrarouge, Nodule, Smears, Building and Construction, Ponctions, [CHIM.INOR]Chemical Sciences/Inorganic chemistry, [CHIM.COOR] Chemical Sciences/Coordination chemistry, [CHIM.ORGA] Chemical Sciences/Organic chemistry, Scanning electron microscopy. Mots-clés. Thyroïde, [CHIM.OTHE] Chemical Sciences/Other, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Electrical and Electronic Engineering, [CHIM.OTHE]Chemical Sciences/Other, Infrared spectroscopy
Abstract: International audience; In this contribution, we have characterized for the first time (to the best of our knowledge), microcalcifications present in fine needle aspiration (FNA) smears of thyroid nodules. Abnormal deposits were analysed through Fourier Transform Infrared Spectroscopy (FTIR) and Field Emission Scanning Electron Microscopy (FE-SEM) in order to obtain their chemical composition as well as their morphology at the micrometer scale. Thirty-one samples coming from 13 patients were investigated comprising five cases of papillary carcinoma, two of Graves’ disease, and six of adenomatous goitre. The smears were also stained for analysis of the cellular characteristics of these lesions for classifying according to the Bethesda classification. Two mineral species, amorphous and nanocrystallised apatite calcium phosphate, have been identified with very different morphologies. Moreover, FE-SEM observations at the micrometer scale underline the presence of different kinds of abnormal deposits.
Published: 2022

3. Efficient 18.8 T MAS-DNP NMR reveals hidden side chains in amyloid fibrils

Author: Lends, Alons, Birlirakis, Nicolas, Cai, Xinyi, Daskalov, Asen, Shenoy, Jayakrishna, Abdul-Shukkoor, Muhammed Bilal, Berbon, Mélanie, Ferrage, Fabien, Liu, Yangping, Loquet, Antoine, Tan, Kong Ooi, Université de Bordeaux (UB), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Tianjin Medical University, ANR-20-ERC9-0008,PulsedDNP,PulsedDNP: faire progresser la sensibilité RMN au-delà du DNP à ondes continues(2020), ANR-21-CE29-0019,HFPulsedDNP,Polarisation Nucléaire Dynamique Pulsée à Haut Champ(2021), and European Project: 639020,H2020,ERC-2014-STG,Weakinteract(2015)
Subjects: Dynamic Nuclear Polarization, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Amyloid Fibrils, Solid-State NMR
Abstract: International audience; Amyloid fibrils are large and insoluble protein assemblies composed of a rigid core associated with a cross-beta arrangement rich in beta-sheet structural elements. It has been widely observed in solid-state NMR experiments that semi-rigid protein segments or side chains do not yield easily observable NMR signals at room temperature. The reasons for the missing peaks may be due to the presence of unfavorable dynamics that interfere with NMR experiments, which result in very weak or unobservable NMR signals. Therefore, for amyloid fibrils, semi-rigid and dynamically disordered segments flanking the amyloid core are very challenging to study. Here, we show that high-field dynamic nuclear polarization (DNP), an NMR hyperpolarization technique typically performed at low temperatures, can circumvent this issue because (i) the low-temperature environment (~ 100 K) slows down the protein dynamics to escape unfavorable detection regime, (ii) DNP improves the overall NMR sensitivity including flexible side chains, and (iii) efficient cross-effect DNP biradicals (SNAPol-1) optimized for high-field DNP ( 18.8 T) are employed to offer high sensitivity and resolution suitable for biomolecular NMR applications. By combining these factors, we have successfully recorded an unprecedented enhancement factor of ε~50 on amyloid fibrils using an 18.8 T/ 800 MHz magnet. We have compared the DNP efficiencies of M-TinyPol, NATriPol-3, and SNAPol-1 biradicals on amyloid fibrils. We found that SNAPol-1 (with ε~50) outperformed the other two radicals. The MAS DNP experiments revealed signals of flexible side chains previously inaccessible at conventional room-temperature experiments. These results demonstrate the potential of MAS-DNP NMR as a valuable tool for structural investigations of amyloid fibrils, particularly for side chains and dynamically disordered segments otherwise hidden at room temperature.
Published: 2023

4. Identification of a human estrogen receptor α tetrapeptidic fragment with dual antiproliferative and anti-nociceptive action

Author: Baptiste Jouffre, Alexandre Acramel, Mathilde Belnou, Maria Francesca Santolla, Marianna Talia, Rosamaria Lappano, Fariba Nemati, Didier Decaudin, Lucie Khemtemourian, Wang-Qing Liu, Marcello Maggiolini, Alain Eschalier, Christophe Mallet, Yves Jacquot, Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Cibles Thérapeutiques et conception de médicaments (CiTCoM - UMR 8038), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Investigation Pré-clinique (LIP), Institut Curie [Paris], Chimie et Biologie des Membranes et des Nanoobjets (CBMN), and Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Multidisciplinary, [SDV]Life Sciences [q-bio]
Abstract: The synthetic peptide ERα17p (sequence: PLMIKRSKKNSLALSLT), which corresponds to the 295–311 region of the human estrogen receptor α (ERα), induces apoptosis in breast cancer cells. In mice and at low doses, it promotes not only the decrease of the size of xenografted triple-negative human breast tumors, but also anti-inflammatory and anti-nociceptive effects. Recently, we have shown that these effects were due to its interaction with the seven-transmembrane G protein-coupled estrogen receptor GPER. Following modeling studies, the C-terminus of this peptide (sequence: NSLALSLT) remains compacted at the entrance of the GPER ligand-binding pocket, whereas its N-terminus (sequence: PLMI) engulfs in the depth of the same pocket. Thus, we have hypothesized that the PLMI motif could support the pharmacological actions of ERα17p. Here, we show that the PLMI peptide is, indeed, responsible for the GPER-dependent antiproliferative and anti-nociceptive effects of ERα17p. By using different biophysical approaches, we demonstrate that the NSLALSLT part of ERα17p is responsible for aggregation. Overall, the tetrapeptide PLMI, which supports the action of the parent peptide ERα17p, should be considered as a hit for the synthesis of new GPER modulators with dual antiproliferative and anti-nociceptive actions. This study highlights also the interest to modulate GPER for the control of pain.
Published: 2023

5. Charge-Driven Arrested Phase-Separation of Polyelectrolyte-Gold Nanoparticle Assemblies Leading to Plasmonic Oligomers

Author: Florent Voisin, Gérald Lelong, Jean Michel Guigner, Thomas Bizien, Jean Maurice Mallet, Florent Carn, Institut de minéralogie et de physique des milieux condensés (IMPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Institut de Physique du Globe de Paris (IPG Paris)-Centre National de la Recherche Scientifique (CNRS), Beamline SWING, Synchrotron SOLEIL, Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Matière et Systèmes Complexes (MSC (UMR_7057)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), IMPMC_Propriétés des amorphes, liquides et minéraux (IMPMC_PALM), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Lelong, Gerald, Matière et Systèmes Complexes (MSC), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Propriétés des amorphes, liquides et minéraux [IMPMC] (IMPMC_PALM), ANR-10-LABX-0096,SEAM,Science and Engineering for Advanced Materials and devices(2010), and ANR-18-CE06-0006,COLIGOMERE,Oligomères colloidaux plasmoniques(2018)
Subjects: Ions, Chitosan, [CHIM.MATE] Chemical Sciences/Material chemistry, Metal Nanoparticles, [CHIM.MATE]Chemical Sciences/Material chemistry, Polyelectrolyte, Polyelectrolytes, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Biomaterials, Self-Assembly, Colloid and Surface Chemistry, Nanoparticle, Complexation, Gold, Particle Size
Abstract: International audience; Aggregates of charged metal particles obtained by electrostatic coupling with a compound of opposite charge in the vicinity of the net zero charge ratio are of interest in the field of plasmonics because the inter-particle distance is minimal, which favours plasmonic coupling. However, these structures present a low colloidal stability limiting the development of applications. In this article we show that globally neutral aggregates formed by electrostatic complexation of citrate-stabilized gold particles and a quaternized chitosan (i.e., polycation) around the net zero charge ratio could be stabilized at a nanometric size by the subsequent addition of polyelectrolyte chains. Furthermore, the sign of the charge carried by the stabilizing chains determines the sign of the global charge carried by the stabilized complexes. The stabilization is demonstrated in saline environment on a broad pH range as well as in a cell culture media over periods of several days. Contrarily to stabilization by charged particles, our stabilized complexes are found to retain their initial characteristics (i.e. shape, size, internal structure and optical properties) after stabilization. Hence, the plasmonic coupling allows to maximize the optical absorption around the 800 nm wavelength at which the lasers used for thermoplasmonic and surface enhanced Raman scattering analysis operate.
Published: 2023

6. Effect of amphiphilic environment on the solution structure of mouse TSPO translocator protein

Author: Sophie Combet, Françoise Bonneté, Stéphanie Finet, Alexandre Pozza, Christelle Saade, Anne Martel, Alexandros Koutsioubas, Jean-Jacques Lacapère, Laboratoire Léon Brillouin (LLB - UMR 12), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), LLB - Matière molle et biophysique (MMB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biologie physico-chimique des protéines membranaires (LBPC-PM (UMR_7099)), Institut de biologie physico-chimique (IBPC (FR_550)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Mécanique et d'Acoustique [Marseille] (LMA ), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Institut Laue-Langevin (ILL), Jülich Centre for Neutron Science (JCNS), Forschungszentrum Jülich GmbH at Heinz Maier-Leibnitz Zentrum (MLZ), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and CNRS (MITI 2021 and Tremplin@ INP 2021)
Subjects: [SDV]Life Sciences [q-bio], ddc:540, General Medicine, Biochemistry
Abstract: International audience; The translocator protein (TSPO) is a ubiquitous transmembrane protein of great pharmacological interest thanks to its high affinity to many drug ligands. The only high-resolution 3D-structure known for mammalian TSPO was obtained by NMR for the mouse mTSPO in DPC detergent only in presence of the high-affinity PK 11195 ligand. An atomic structure of free-ligand mTSPO is still missing to better understand the interaction of ligands with mTSPO and their effects on the protein conformation.Here, we decipher the solution structures of the recombinant mTSPO without ligand both in (i) SDS, the detergent used to extract and purify the protein from E. coli inclusion bodies, and (ii) DPC, the detergent used to solve the PK 11195-binding mTSPO NMR structure.We report partially refolded and less flexible mTSPO helices in DPC compared to SDS. Besides, DPC stabilizes the tertiary structure of mTSPO, as shown by a higher intrinsic Trp fluorescence and changes in indole environment.We evaluate by SEC-MALLS that ∼135 SDS and ∼100 DPC molecules are bound to mTSPO. SEC-small-angle X-ray (SAXS) and neutron (SANS) scattering confirm a larger mTSPO-detergent complex in SDS than in DPC. Using the contrast-matching technique in SEC-SANS, we demonstrate that mTSPO conformation is more compact and less flexible in DPC than in SDS. Combining ab initio modeling with SANS, we confirm that mTSPO conformation is less elongated in DPC than in SDS. However, the free-ligand mTSPO envelope in DPC is not as compact as the PK 11195-binding protein NMR structure, the ligand stiffening the protein.
Published: 2023

7. Visualizing protein breathing motions associated with aromatic ring flipping

Author: Laura Mariño Pérez, Francesco S. Ielasi, Luiza M. Bessa, Damien Maurin, Jaka Kragelj, Martin Blackledge, Nicola Salvi, Guillaume Bouvignies, Andrés Palencia, Malene Ringkjøbing Jensen, Universitat de les Illes Balears (UIB), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), University of Texas Southwestern Medical Center [Dallas], Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), HAL-SU, Gestionnaire, and ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017)
Subjects: src Homology Domains, Motion, Multidisciplinary, Protein Conformation, [CHIM.CRIS]Chemical Sciences/Cristallography, Proteins, Tyrosine, [CHIM.CRIS] Chemical Sciences/Cristallography, Crystallography, X-Ray, Solution-state NMR, Nuclear Magnetic Resonance, Biomolecular, X-ray crystallography
Abstract: Aromatic residues cluster in the core of folded proteins, where they stabilize the structure through multiple interactions. Nuclear magnetic resonance (NMR) studies in the 1970s showed that aromatic side chains can undergo ring flips—that is, 180° rotations—despite their role in maintaining the protein fold1–3. It was suggested that large-scale ‘breathing’ motions of the surrounding protein environment would be necessary to accommodate these ring flipping events1. However, the structural details of these motions have remained unclear. Here we uncover the structural rearrangements that accompany ring flipping of a buried tyrosine residue in an SH3 domain. Using NMR, we show that the tyrosine side chain flips to a low-populated, minor state and, through a proteome-wide sequence analysis, we design mutants that stabilize this state, which allows us to capture its high-resolution structure by X-ray crystallography. A void volume is generated around the tyrosine ring during the structural transition between the major and minor state, and this allows fast flipping to take place. Our results provide structural insights into the protein breathing motions that are associated with ring flipping. More generally, our study has implications for protein design and structure prediction by showing how the local protein environment influences amino acid side chain conformations and vice versa.
Published: 2022

8. CADPS functional mutations in patients with bipolar disorder increase the sensitivity to stress

Author: Jérémy Sitbon, Dennis Nestvogel, Caroline Kappeler, Aude Nicolas, Stephanie Maciuba, Annabelle Henrion, Réjane Troudet, Elisa Courtois, Gaël Grannec, Violaine Latapie, Caroline Barau, Philippe Le Corvoisier, Nicolas Pietrancosta, Chantal Henry, Marion Leboyer, Bruno Etain, Marika Nosten-Bertrand, Thomas F. J. Martin, JeongSeop Rhee, Stéphane Jamain, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fondation FondaMental [Créteil], Max Planck Institute of Experimental Medicine [Göttingen] (MPI), Max-Planck-Gesellschaft, University of Wisconsin-Madison, Institut du Fer à Moulin (IFM - Inserm U1270 - SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Plateforme de Ressources Biologiques [Henri Mondor AP-HP, Créteil] (PRB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Université Sorbonne Paris Cité (USPC), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), IMRB - 'NeuroPsychologie Interventionnelle' [Créteil] (U955 Inserm - UPEC), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Systèmes glutamatergiques normaux et pathologiques = Normal and Pathologic Glutamatergic Neurons (NPS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Analyse, Interactions Moléculaires et Cellulaires (LBM-E2), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Chimie Moléculaire de Paris Centre (FR 2769), and Jamain, Stéphane
Subjects: Bipolar Disorder, Neuronal Plasticity, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Calcium-Binding Proteins, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Vesicular Transport Proteins, Nerve Tissue Proteins, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Exocytosis, Mice, Cellular and Molecular Neuroscience, Psychiatry and Mental health, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Mutation, Animals, Humans, Calcium, Molecular Biology
Abstract: International audience; Bipolar disorder is a severe and chronic psychiatric disease resulting from a combination of genetic and environmental risk factors. Here, we identified a significant higher mutation rate in a gene encoding the calcium-dependent activator protein for secretion (CADPS) in 132 individuals with bipolar disorder, when compared to 184 unaffected controls or to 21,070 non-psychiatric and non-Finnish European subjects from the Exome Aggregation Consortium. We found that most of these variants resulted either in a lower abundance or a partial impairment in one of the basic functions of CADPS in regulating neuronal exocytosis, synaptic plasticity and vesicular transporter-dependent uptake of catecholamines. Heterozygous mutant mice for Cadps+/- revealed that a decreased level of CADPS leads to manic-like behaviours, changes in BDNF level and a hypersensitivity to stress. This was consistent with more childhood trauma reported in families with mutation in CADPS, and more specifically in mutated individuals. Furthermore, hyperactivity observed in mutant animals was rescued by the mood-stabilizing drug lithium. Overall, our results suggest that dysfunction in calcium-dependent vesicular exocytosis may increase the sensitivity to environmental stressors enhancing the risk of developing bipolar disorder.
Published: 2022

9. An expanded palette of fluorogenic HaloTag probes with enhanced contrast for targeted cellular imaging

Author: Sylvestre P. J. T. Bachollet, Yuriy Shpinov, Fanny Broch, Hela Benaissa, Arnaud Gautier, Nicolas Pietrancosta, Jean-Maurice Mallet, Blaise Dumat, Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Systèmes glutamatergiques normaux et pathologiques = Normal and Pathologic Glutamatergic Neurons (NPS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Analyse, Interactions Moléculaires et Cellulaires (LBM-E2), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Chimie Moléculaire de Paris Centre (FR 2769), ANR-18-CE44-0006,DIPimaging,Sondes fluorogéniques à double détection pour l'imagerie biphotonique localisée(2018), Dumat, Blaise, and APPEL À PROJETS GÉNÉRIQUE 2018 - Sondes fluorogéniques à double détection pour l'imagerie biphotonique localisée - - DIPimaging2018 - ANR-18-CE44-0006 - AAPG2018 - VALID
Subjects: Hydrolases, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, Proteins, Molecular Dynamics Simulation, HaloTag, [CHIM.ORGA] Chemical Sciences/Organic chemistry, Fluorogenic probes, Biochemistry, Fluorescence imaging, molecular rotors, embryonic structures, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Physical and Theoretical Chemistry, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Fluorescent Dyes
Abstract: International audience; We report the development of HaloTag fluorogens based on dipolar flexible molecular rotor structures. By modulating the electron donating and withdrawing groups, we have tuned the absorption and emission wavelengths to design a palette of fluorogens with emissions spanning the green to red range, opening new possibilities for multicolor imaging. The probes were studied in glycerol and in presence of HaloTag and exhibited good fluorogenic properties thanks to a viscosity-sensitive emission. In live-cell confocal imaging, the fluorogens yielded only a very low non-specific signal that enabled wash-free targeted imaging of intracellular organelles and proteins with good contrast. Combining experimental studies and theoretical investigation of the protein/fluorogen complexes by molecular dynamics, these results offer new insight into the design of molecular rotor-based fluorogenic HaloTag probes in order to improve reaction rates and the imaging contrast.
Published: 2022

10. Long-lived states of methylene protons in achiral molecules

Author: Anna Sonnefeld, Aiky Razanahoera, Philippe Pelupessy, Geoffrey Bodenhausen, Kirill Sheberstov, Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and European Project: 951459,HISCORE
Subjects: Multidisciplinary, [CHIM]Chemical Sciences
Abstract: In nuclear magnetic resonance (NMR), the lifetimes of long-lived states (LLSs) are exquisitely sensitive to their environment. However, the number of molecules where such states can be excited has hitherto been rather limited. Here, it is shown that LLSs can be readily excited in many common molecules that contain two or more neighboring CH 2 groups. Accessing such LLSs does not require any isotopic enrichment, nor does it require any stereogenic centers to lift the chemical equivalence of CH 2 protons. LLSs were excited in a variety of metabolites, neurotransmitters, vitamins, amino acids, and other molecules. One can excite LLSs in several different molecules simultaneously. In combination with magnetic resonance imaging, LLSs can reveal a contrast upon noncovalent binding of ligands to macromolecules. This suggests new perspectives to achieve high-throughput parallel drug screening by NMR.
Published: 2022

11. GRID1/ GluD1 homozygous variants linked to intellectual disability and spastic paraplegia impair mGlu1/5 receptor signaling and excitatory synapses

Author: Dévina C. Ung, Ludovic Tricoire, Nicolas Pietrancosta, Andjela Zlatanovic, Ben Pode-Shakked, Annick Raas-Rothschild, Orly Elpeleg, Bassam Abu-Libdeh, Nasrin Hamed, Marie-Amélie Papon, Sylviane Marouillat, Rose-Anne Thépault, Giovanni Stevanin, Bertrand Lambolez, Annick Toutain, Régine Hepp, Frédéric Laumonnier, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Systèmes glutamatergiques normaux et pathologiques = Normal and Pathologic Glutamatergic Neurons (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Analyse, Interactions Moléculaires et Cellulaires (LBM-E2), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Chimie Moléculaire de Paris Centre (FR 2769), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Tel Aviv University (TAU), Chaim Sheba Medical Center, Department of Genetics and Metabolic Diseases and the Monique and Jacques Roboh Department of Genetic Research, Hadassah Hebrew University Medical Center [Jerusalem], Institute of Human Genetics, Universität Regensburg (UR), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Institut de Biologie Paris Seine (IBPS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: The ionotropic glutamate delta receptor GluD1, encoded by the GRID1 gene, is involved in synapse formation, function, and plasticity. GluD1 does not bind glutamate, but instead cerebellin and D-serine, which allow the formation of trans-synaptic bridges, and trigger transmembrane signaling. Despite wide expression in the nervous system, pathogenic GRID1 variants have not been characterized in humans so far. We report homozygous missense GRID1 variants in five individuals from two unrelated consanguineous families presenting with intellectual disability and spastic paraplegia, without (p.Thr752Met) or with (p.Arg161His) diagnosis of glaucoma, a threefold phenotypic association whose genetic bases had not been elucidated previously. Molecular modeling indicated that Arg161His and Thr752Met mutations alter the hinge between GluD1 cerebellin and D-serine binding domains and the stiffness of this latter domain, respectively. Expression, trafficking, physical interaction with metabotropic glutamate receptor mGlu1, and cerebellin binding of GluD1 mutants were not conspicuously altered. Conversely, we found that both GluD1 mutants hampered signaling of metabotropic glutamate receptor mGlu1/5 via the ERK pathway in neurons of primary cortical culture. Moreover, both mutants impaired dendrite morphology and excitatory synapse density in neurons of primary hippocampal culture. These results show that the clinical phenotypes are distinct entities segregating in the families as an autosomal recessive trait, and caused by pathophysiological effects of GluD1 mutants involving metabotropic glutamate receptor signaling and neuronal connectivity. Our findings unravel the importance of the GluD1 receptor signaling in sensory, cognitive and motor functions of the human nervous system.
Published: 2022

12. Convergent vews on disordered protein dynamics from NMR and computational approaches

Author: Nicola, Salvi, Vojtěch, Zapletal, Zuzana, Jaseňáková, Milan, Zachrdla, Petr, Padrta, Subhash, Narasimhan, Thorsten, Marquardsen, Jean-Max, Tyburn, Lukáš, Žídek, Martin, Blackledge, Fabien, Ferrage, Pavel, Kadeřávek, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Masaryk University [Brno] (MUNI), Central European Institute of Technology [Brno] (CEITEC MU), Brno University of Technology [Brno] (BUT), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Bruker BioSpin MRI GmbH [Ettlingen, Germany], ANR-18-CE29-0003,NANO-DISPRO,Une méthode intégrative pour déterminer les mouvements nanométriques des protéines désordonnées(2018), Ferrage, Fabien, and APPEL À PROJETS GÉNÉRIQUE 2018 - Une méthode intégrative pour déterminer les mouvements nanométriques des protéines désordonnées - - NANO-DISPRO2018 - ANR-18-CE29-0003 - AAPG2018 - VALID
Subjects: Intrinsically Disordered Proteins, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [CHIM.THEO] Chemical Sciences/Theoretical and/or physical chemistry, Magnetic Resonance Spectroscopy, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Protein Conformation, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Biophysics, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, DNA-Directed RNA Polymerases, Molecular Dynamics Simulation, Amides
Abstract: International audience; Intrinsically disordered proteins (IDPs) or intrinsically disordered regions (IDRs) is a class of biologically important proteins exhibiting specific biophysical characteristics. They lack a hydrophobic core, and their conformational behavior is strongly influenced by electrostatic interactions. IDPs and IDRs are highly dynamic, and a characterization of the motions of IDPs and IDRs is essential for their physically correct description. NMR together with molecular dynamics simulations are the methods best suited to such a task because they provide information about dynamics of proteins with atomistic resolution. Here, we present a study of motions of a disordered C-terminal domain of the delta subunit of RNA polymerase from Bacillus subtilis. Positively and negatively charged residues in the studied domain form transient electrostatic contacts critical for the biological function. Our study is focused on investigation of ps-ns dynamics of backbone of the delta subunit based on analysis of amide 15N NMR relaxation data and molecular dynamics simulations. In order to extend an informational content of NMR data to lower frequencies, which are more sensitive to slower motions, we combined standard (high-field) NMR relaxation experiments with high-resolution relaxometry. Altogether, we collected data reporting the relaxation at 12 different magnetic fields, resulting in an unprecedented data set. Our results document that the analysis of such data provides a consistent description of dynamics and confirms the validity of so far used protocols of the analysis of dynamics of IDPs also for a partially folded protein. In addition, the potential to access detailed description of motions at the timescale of tens of ns with the help of relaxometry data is discussed. Interestingly, in our case, it appears to be mostly relevant for a region involved in the formation of temporary contacts within the disordered region, which was previously proven to be biologically important.
Published: 2022

13. Targeting hIAPP fibrillation: A new paradigm to prevent β-cell death?

Author: Ghislaine Guillemain, Jean-Jacques Lacapere, Lucie Khemtemourian, Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and khemtemourian, lucie
Subjects: Inflammation, Amyloid, Cell Death, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV]Life Sciences [q-bio], Cross-fibrils, Biophysics, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Type 2 diabetes, Cell Biology, Biochemistry, Islet Amyloid Polypeptide, β-Cells, Amyloid proteins, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [SDV] Life Sciences [q-bio], Diabetes Mellitus, Type 2, Humans, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Pancreas, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]
Abstract: International audience; Loss of pancreatic β-cell mass is deleterious for type 2 diabetes patients since it reduces insulin production, critical for glucose homeostasis. The main research axis developed over the last few years was to generate new pancreatic β-cells or to transplant pancreatic islets as occurring for some specific type 1 diabetes patients. We evaluate here a new paradigm consisting in preservation of β-cells by prevention of human islet amyloid polypeptide (hIAPP) oligomers and fibrils formation leading to pancreatic β-cell death. We review the hIAPP physiology and the pathology that contributes to β-cell destruction, deciphering the various cellular steps that could be involved. Recent progress in understanding other amyloidosis such as Aβ, Tau, α-synuclein or prion, involved in neurodegenerative processes linked with inflammation, has opened new research lines of investigations to preserve neuronal cells. We evaluate and estimate their transposition to the pancreatic β-cells preservation. Among them is the control of reactive oxygen species (ROS) production occurring with inflammation and the possible implication of the mitochondrial translocator protein as a diagnostic and therapeutic target. The present review also focuses on other amyloid forming proteins from molecular to physiological and physiopathological points of view that could help to better decipher hIAPP-induced β-cell death mechanisms and to prevent hIAPP fibril formation.
Published: 2022

14. Ligand‐Directed Modification of Active Matrix Metalloproteases: Activity‐based Probes with no Photolabile Group

Author: Marion Doladilhe, Vincent Dive, Olivier Lequin, Pierrick Bruyat, Monika Kaminska, Dimitris Georgiadis, Carole Fruchart Gaillard, Mélissa De Souza, Robert Thai, Evelyne Cassar-Lajeunesse, Carole Malgorn, Laurent Devel, Andrzej Galat, Fabrice Beau, Sarah Bregant, Isabelle Correia, Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO) (SIMoS), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département de Chimie Moléculaire (DCM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Athens, Athens, ANR-18-CE44-0012,ProMaP,Nouvelles sondes pour la détection de Métallo protéases par spectrométrie de masse(2018), and ANR-10-LABX-0033,LERMIT,Research Laboratory on Drugs and Therapeutic Innovation(2010)
Subjects: biology, Proteomic Profiling, Chemistry, Active site, General Chemistry, General Medicine, Matrix metalloproteinase, Ligand (biochemistry), biology.organism_classification, Catalysis, law.invention, Biochemistry, Covalent bond, law, Proteome, biology.protein, Recombinant DNA, [CHIM]Chemical Sciences, Eukaryote
Abstract: International audience; Activity-based probes enable discrimination between the active enzyme and its inactive or inactivated counterparts. Since metalloproteases catalysis is non-covalent, activity-based probes targeting them have been systematically developed by decorating reversible inhibitors with photo-crosslinkers. By exploiting two types of ligand-guided chemistry, we identified novel activity-based probes capable of covalently modifying the active site of matrix metalloproteases (MMPs) without any external trigger. The ability of these probes to label recombinant MMPs was validated in vitro and the identity of the main labelling sites within their S$_3$′ region unambiguously assigned. We also demonstrated that our affinity probes can react with rhMMP12 at nanogram scale (that is, at 0.07 % (w/w)) in complex proteomes. Finally, this ligand-directed chemistry was successfully applied to label active MMP-12 secreted by eukaryote cells. We believe that this approach could be transferred more widely to many other metalloproteases, thus contributing to tackle their unresolved proteomic profiling in vivo.
Published: 2021

15. Nanoscopic distribution of VAChT and VGLUT3 in striatal cholinergic varicosities suggests colocalization and segregation of the two transporters in synaptic vesicles

Author: Paola Cristofari, Mazarine Desplanque, Odile Poirel, Alison Hébert, Sylvie Dumas, Etienne Herzog, Lydia Danglot, David Geny, Jean-François Gilles, Audrey Geeverding, Susanne Bolte, Alexis Canette, Michaël Trichet, Véronique Fabre, Stéphanie Daumas, Nicolas Pietrancosta, Salah El Mestikawy, Véronique Bernard, Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Systèmes glutamatergiques normaux et pathologiques = Normal and Pathologic Glutamatergic Neurons (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Oramacell [Paris, France], Interdisciplinary Institute for Neuroscience (IINS), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Microscopie Electronique [IBPS] (IBPS-ME), Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Imagerie Cellulaire et Cytométrie de Flux [IBPS] (IBPS-IP), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), McGill University = Université McGill [Montréal, Canada], and Bernard, Veronique
Subjects: striatal cholinergic interneurons, vesicular acetylcholine transporter, VGLUT3, Type 3 vesicular glutamate transporter, Striatum, STimulated Emission Depletion microscopy (STED), Cellular and Molecular Neuroscience, VAChT, Quantitative Biology - Neurons and Cognition, FOS: Biological sciences, acetylcholine-glutamate cotransmission, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurons and Cognition (q-bio.NC), [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], scanning electron microscopy (SEM), Molecular Biology
Abstract: International audience; Striatal cholinergic interneurons (CINs) use acetylcholine (ACh) and glutamate (Glut) to regulate the striatal network since they express vesicular transporters for ACh (VAChT) and Glut (VGLUT3). However, whether ACh and Glut are released simultaneously and/or independently from cholinergic varicosities is an open question. The answer to that question requires the multichannel detection of vesicular transporters at the level of single synaptic vesicle (SV). Here, we used super-resolution STimulated Emission Depletion microscopy (STED) to characterize and quantify the distribution of VAChT and VGLUT3 in CINs SVs. Nearest-neighbor distances analysis between VAChT and VGLUT3-immunofluorescent spots revealed that 34% of CINs SVs contain both VAChT and VGLUT3. In addition, 40% of SVs expressed only VAChT while 26% of SVs contain only VGLUT3. These results suggest that SVs from CINs have the potential to store simultaneously or independently ACh and/or Glut. Overall, these morphological findings support the notion that CINs varicosities can signal with either ACh or Glut or both with an unexpected level of complexity.
Published: 2022

16. Phenyl Silicates with Substituted Catecholate Ligands: Synthesis, Structural Studies and Reactivity

Author: Heng-Rui Zhang, Etienne Derat, Louis Fensterbank, Aurélie Bernard, Etienne Levernier, Khaoula Jaouadi, Geoffrey Gontard, Laurence Grimaud, Cyril Ollivier, Vincent Corcé, Claire Troufflard, Institut Parisien de Chimie Moléculaire (IPCM), Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des biomolécules (LBM UMR 7203), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Méthodes et Application en Chimie Organique (MACO), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Chimie Moléculaire de Paris Centre (FR 2769), and Ollivier, Cyril
Subjects: chemistry.chemical_classification, 010405 organic chemistry, Chemistry, Ligand, Aryl, Radical, Organic Chemistry, Photoredox catalysis, General Chemistry, 010402 general chemistry, 01 natural sciences, Medicinal chemistry, Catalysis, 0104 chemical sciences, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, [CHIM.THEO] Chemical Sciences/Theoretical and/or physical chemistry, chemistry.chemical_compound, Moiety, Reactivity (chemistry), Alkyl
Abstract: International audience; While the generation of aryl radicals by photoredox catalysis is well-documented under reductive conditions, it has remained challenging under an oxidative pathway. Because of the easy photooxidation of alkyl bis-catecholato silicates, a general study on phenyl silicates bearing substituted catecholate ligands has been achieved. The newly synthesized phenyl silicates have been fully characterized and their reactivity has been explored. It was found that thanks to the substitution of the catecholate moiety and notably with the 4-cyanocatecholato ligand, the phenyl radical could be generated and trapped. Computational studies provided a rationale for these findings.
Published: 2021

17. Dissection of the anti-Candida albicans mannan immune response using synthetic oligomannosides reveals unique properties of β-1,2 mannotriose protective epitopes

Author: Sébastien Damiens, Faustine Dubar, Samir Jawhara, Boualem Sendid, Mayeul Collot, Karine Lecointe, Jean-Maurice Mallet, Anne-Sophie Drucbert, Daniel Poulain, Chantal Fradin, Pierre-Marie Danzé, Jean-Pierre Vilcot, Jérôme de Ruyck, Frédéric Grenouillet, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Optoélectronique - IEMN (OPTO - IEMN), INSA Institut National des Sciences Appliquées Hauts-de-France (INSA Hauts-De-France), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), We thank the European Union for funding through the INTERREG V France—Wallonie—Vlaanderen program—SmartBioControl-BIOSENS project and the Programme Hospitalier de Recherche Clinique, CandiGene, 2011–1918., Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire des biomolécules [LBM UMR 7203], Institut de Pathologie [CHU Lille], Laboratoire de Bioimagerie et Pathologies [LBP], Médicaments et biomatériaux à libération contrôlée: mécanismes et optimisation - Advanced Drug Delivery Systems - U 1008 [MBLC - ADDS], Lille Inflammation Research International Center - U 995 [LIRIC], Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 [IEMN], Laboratoire Chrono-environnement (UMR 6249) [LCE], Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF], and Collot, Mayeul
Subjects: Antigens, Fungal, medicine.drug_class, [SDV]Life Sciences [q-bio], Science, Immunology, Oligosaccharides, Monoclonal antibody, Biochemistry, Microbiology, Article, Epitope, Mannans, 03 medical and health sciences, Antigen, Antibody Specificity, Candida albicans, medicine, 030304 developmental biology, Mannan, 0303 health sciences, Multidisciplinary, biology, 030306 microbiology, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Candidiasis, Antibodies, Monoclonal, Surface Plasmon Resonance, [CHIM.ORGA] Chemical Sciences/Organic chemistry, biology.organism_classification, Chemical biology, Corpus albicans, 3. Good health, [SDV] Life Sciences [q-bio], Polyclonal antibodies, biology.protein, Medicine, Antibody, Trisaccharides, Epitope Mapping
Abstract: Candida albicans mannan consists of a large repertoire of oligomannosides with different types of mannose linkages and chain lengths, which act as individual epitopes with more or less overlapping antibody specificities. Although anti-C. albicans mannan antibody levels are monitored for diagnostic purposes nothing is known about the qualitative distribution of these antibodies in terms of epitope specificity. We addressed this question using a bank of previously synthesized biotin sulfone tagged oligomannosides (BSTOs) of α and β anomery complemented with a synthetic β-mannotriose described as a protective epitope. The reactivity of these BSTOs was analyzed with IgM isotype monoclonal antibodies (MAbs) of known specificity, polyclonal sera from patients colonized or infected with C. albicans, and mannose binding lectin (MBL). Surface plasmon resonance (SPR) and multiple analyte profiling (MAP) were used. Both methods confirmed the usual reactivity of MAbs against either α or β linkages, excepted for MAb B6.1 (protective epitope) reacting with β-Man whereas the corresponding BSTO reacted with anti-α-Man. These results were confirmed in western blots with native C. albicans antigens. Using patients’ sera in MAP, a significant correlation was observed between the detection of anti-mannan antibodies recognizing β- and α-Man epitopes and detection of antibodies against β-linked mannotriose suggesting that this epitope also reacts with human polyclonal antibodies of both specificities. By contrast, the reactivity of human sera with other α- and β-linked BSTOs clearly differed according to their colonized or infected status. In these cases, the establishment of an α/β ratio was extremely discriminant. Finally SPR with MBL, an important lectin of innate immunity to C. albicans, classically known to interact with α-mannose, also interacted in an unexpected way with the protective epitope. These cumulative data suggest that structure/activity investigations of the finely tuned C. albicans anti-mannose immune response are worthwhile to increase our basic knowledge and for translation in medicine.
Published: 2021

18. Electrochemical TEMPO-Catalyzed Oxidative Ugi-Type Reaction

Author: Na Pan, Maegan Xinen Lee, Maxime R. Vitale, Laurence Grimaud, Louis Bunel, Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), East China Normal University [Shangaï] (ECNU), and VITALE, Maxime R.
Subjects: Cultural Studies, History, Literature and Literary Theory, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Chemistry, Isocyanide, Organic chemistry, Oxidative phosphorylation, [CHIM.ORGA] Chemical Sciences/Organic chemistry, Electrosynthesis, Electrochemistry, Combinatorial chemistry, Indirect anodic oxidation, Catalysis, chemistry.chemical_compound, QD241-441, Oxidative Ugi reaction, TEMPO, human activities, Inorganic chemistry, Muticomponent reaction, QD146-197
Abstract: International audience; Oxidative isocyanide-based multicomponent reactions (oxidative IMCRs) are very useful tools for the rapid construction of molecular diversity starting from readily available and stable substrates. Despite all their benefits, such multicomponent reactions are underdeveloped and strictly limited to 3component processes. Indeed, in the presence of several reaction partners, the oxidation event needs to be rigorously chemoselective, which becomes incredibly more intricate as the number of reactive components increases. Nonetheless, we could overcome this significant pitfall and reach the first oxidative Ugi-type 4-IMCR by capitalizing on a very mild and green TEMPO-catalyzed electro-oxidation process. Employing alcohols as aldehyde surrogates and in the notable absence of any supporting electrolyte, this transformation proved to be extremely chemoselective in the presence of an amine and was compatible with a wide range of alcohols, amines, isocyanides, and carboxylic acids.
Published: 2021

19. How does it really move? Recent progress in the investigation of protein nanosecond dynamics by NMR and simulation

Author: Olof Stenström, Candide Champion, Marc Lehner, Guillaume Bouvignies, Sereina Riniker, Fabien Ferrage, Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Chemistry and Applied Biosciences [ETH Zürich] (D-CHAB), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), and Ferrage, Fabien
Subjects: Magnetic Resonance Spectroscopy, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Molecular dynamics simulations, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Protein dynamics, Molecular Dynamics Simulation, NMR spectroscopy, NMR relaxation, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [CHIM.THEO] Chemical Sciences/Theoretical and/or physical chemistry, Motion, Structural Biology, Molecular Biology, Nuclear Magnetic Resonance, Biomolecular
Abstract: Nuclear magnetic resonance (NMR) spin relaxation experi-ments currently probe molecular motions on timescales from picoseconds to nanoseconds. The detailed interpretation of these motions in atomic detail benefits from complementarity with the results from molecular dynamics (MD) simulations. In this mini-review, we describe the recent developments in experimental techniques to study the backbone dynamics from 15N relaxation and side-chain dynamics from 13C relaxation, discuss the different analysis approaches from model-free to dynamics detectors, and highlight the many ways that NMR relaxation experiments and MD simulations can be used together to improve the interpretation and gain insights into protein dynamics. ISSN:0959-440X ISSN:1879-033X
Published: 2022

20. Structural Bases for the Involvement of Phosphatidylinositol-4,5-bisphosphate in the Internalization of the Cell-Penetrating Peptide Penetratin

Author: Leïla Bechtella, Edward Chalouhi, Paula Milán Rodríguez, Marine Cosset, Delphine Ravault, Françoise Illien, Sandrine Sagan, Ludovic Carlier, Olivier Lequin, Patrick F. J. Fuchs, Emmanuelle Sachon, Astrid Walrant, Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Analyse, Interactions Moléculaires et Cellulaires (LBM-E2), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Chimie Moléculaire de Paris Centre (FR 2769), Spectrométrie de masse de Sorbonne Université [IBPS] (MS3U), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Walrant, Astrid
Subjects: [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Medicine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, General Medicine, Cell-Penetrating Peptides, Carrier Proteins, Phosphatidylinositols, Biochemistry, Protein Binding
Abstract: International audience; Cell-penetrating peptides cross cell membranes through various parallel internalization pathways. Herein, we analyze the role of the negatively charged lipid phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) in the internalization of Penetratin. Contributions of both inner leaflet and outer leaflet pools of PI(4,5)P2 were revealed by quantifying the internalization of Penetratin in cells treated with PI(4,5)P2 binders. Studies on model systems showed that Penetratin has a strong affinity for PI(4,5)P2, and interacts selectively with this lipid, even in the presence of other negatively charged lipids, as demonstrated by affinity photocrosslinking experiments. Differential scanning calorimetry experiments showed that Penetratin induces lateral segregation in PI(4,5)P2-containing liposomes, which was confirmed by coarse-grained molecular dynamics simulations. NMR experiments indicated that Penetratin adopts a stabilized helical conformation in the presence of PI(4,5)P2-containing membranes, with an orientation parallel to the bilayer plane, which was also confirmed by all-atom simulations. NMR and photocrosslinking experiments also suggest a rather shallow insertion of the peptide in the membrane. Put together, our findings suggest that PI(4,5)P2 is a privileged interaction partner for Penetratin and that it plays an important role in Penetratin internalization.
Published: 2022

21. Monitoring In Vivo Performances of Protein–Drug Conjugates Using Site-Selective Dual Radiolabeling and Ex Vivo Digital Imaging

Author: Héloïse Cahuzac, Antoine Sallustrau, Carole Malgorn, Fabrice Beau, Peggy Barbe, Victor Babin, Steven Dubois, Alberto Palazzolo, Robert Thai, Isabelle Correia, Ki Baek Lee, Sébastien Garcia-Argote, Olivier Lequin, Mathilde Keck, Hervé Nozach, Sophie Feuillastre, Xin Ge, Gregory Pieters, Davide Audisio, Laurent Devel, Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO) (SIMoS), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Chimie Bio-Organique et de Marquage (SCBM), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and The University of Texas Health Science Center at Houston (UTHealth)
Subjects: Immunoconjugates, [SDV]Life Sciences [q-bio], Drug Discovery, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Molecular Medicine, Carbon Radioisotopes, Article
Abstract: International audience; In preclinical models, the development and optimization of protein−drug conjugates require accurate determination of the plasma and tissue profiles of both the protein and its conjugated drug. To this aim, we developed a bioanalytical strategy based on dual radiolabeling and ex vivo digital imaging. By combining enzymatic and chemical reactions, we obtained homogeneous dual-labeled anti-MMP-14 Fabs (antigen-binding fragments) conjugated to monomethyl auristatin E where the protein scaffold was labeled with carbon-14 (14C) and the conjugated drug with tritium (3H). These antibody−drug conjugates with either a noncleavable or a cleavable linker were then evaluated in vivo. By combining liquid scintillation counting and ex vivo dual-isotope radio-imaging, it was possible not only to monitor both components simultaneously during their circulation phase but also to quantify accurately their amount accumulated within the different organs.
Published: 2022

22. Explicit models of motions to understand protein side-chain dynamics

Author: Nicolas Bolik-Coulon, Olivier Languin-Cattoën, Diego Carnevale, Milan Zachrdla, Damien Laage, Fabio Sterpone, Guillaume Stirnemann, Fabien Ferrage, Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biochimie théorique [Paris] (LBT (UPR_9080)), Institut de biologie physico-chimique (IBPC (FR_550)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Processus d'Activation Sélective par Transfert d'Energie Uni-électronique ou Radiatif (UMR 8640) (PASTEUR), Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Ferrage, Fabien
Subjects: Diffusion, Chemical Physics (physics.chem-ph), [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Motion, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Entropy, Physics - Chemical Physics, General Physics and Astronomy, FOS: Physical sciences, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Molecular Dynamics Simulation
Abstract: International audience; Nuclear magnetic relaxation is widely used to probe protein dynamics. For decades, most analyses of relaxation in proteins have relied successfully on the model-free approach, forgoing mechanistic descriptions of motions. Model-free types of correlation functions cannot describe a large carbon-13 relaxation dataset in protein sidechains. Here, we use molecular dynamics simulations to design explicit models of motion and solve Fokker-Planck diffusion equations. These models of motion provide better agreement with relaxation data, mechanistic insight and a direct link to configuration entropy.
Published: 2022

23. Conjugation of Oligo-His Peptides to Magnetic γ-Fe 2 O 3 @SiO 2 Core–Shell Nanoparticles Promotes Their Access to the Cytosol

Author: Mathilde Le Jeune, Emilie Secret, Michaël Trichet, Aude Michel, Delphine Ravault, Françoise Illien, Jean-Michel Siaugue, Sandrine Sagan, Fabienne Burlina, Christine Ménager, PHysicochimie des Electrolytes et Nanosystèmes InterfaciauX (PHENIX), Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Microscopie Electronique [IBPS] (IBPS-ME), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Analyse, Interactions Moléculaires et Cellulaires (LBM-E2), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Chimie Moléculaire de Paris Centre (FR 2769), Département de Sciences sociales ENS-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Sorbonne Université (SU), and Secret, Emilie
Subjects: [SDV] Life Sciences [q-bio], cell-penetrating peptides, magnetic core-shell nanoparticles, [SDV]Life Sciences [q-bio], [CHIM] Chemical Sciences, cationic peptides, click chemistry, [CHIM]Chemical Sciences, General Materials Science, endosomal escape
Abstract: International audience; The endosomal entrapment of functional nanoparticles is a severe limitation to their use for biomedical applications. In the case of magnetic nanoparticles (MNPs), this entrapment leads to poor heating efficiency for magnetic hyperthermia and suppresses the possibility to manipulate them in the cytosol. Current strategies to limit their entrapment are based on their functionalization with cell-penetrating peptides in order to promote their translocation directly across the cell membrane or their endosomal escape. However, these strategies suffer from potential release of free peptides in cell and to the best of our knowledge there is currently a lack of effective methods for the cytosolic delivery of MNPs after incubation with cells. Herein, we report the conjugation of fluorescently labelled cationic peptides to γ-Fe2O3@SiO2 core-shell nanoparticles by click chemistry to improve MNP access to the cytosol. We compare the effect of Arg9 and His4 peptides. On one hand, Arg9 is a classical cell-penetrating peptide, able to enter cells by direct translocation and on the other hand, it has been demonstrated that sequences rich in histidine residues promote endosomal escape, most probably by the proton sponge effect. The methodology developed allows to have a high co-localization of the peptides and core-shell nanoparticles in cells and to attest that the grafting onto nanoparticles of peptides rich in histidine promotes NP access to the cytosol. The endosomal escape was confirmed by a calcein leakage assay and by ultrastructural analysis in transmission electron microscopy. No toxicity of the nanoparticles functionalized with peptides was found. We show that our conjugation strategy is compatible with the addition of multiple substrates and can thus be used for the delivery of cytoplasm-targeted therapeutics.
Published: 2022

24. SOD mimics: From the tool box of the chemists to cellular studies

Author: Clotilde Policar, Jean Bouvet, Hélène C. Bertrand, Nicolas Delsuc, Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL), Sorbonne Université (SU), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Policar, Clotilde
Subjects: [CHIM.INOR] Chemical Sciences/Inorganic chemistry, Superoxide Dismutase, [CHIM.ORGA]Chemical Sciences/Organic chemistry, [CHIM.INOR]Chemical Sciences/Inorganic chemistry, [CHIM.COOR] Chemical Sciences/Coordination chemistry, [CHIM.ORGA] Chemical Sciences/Organic chemistry, Biochemistry, Catalysis, Analytical Chemistry, Cellular studies, Design of metallodrugs, Biomimetic Materials, Coordination Complexes, Superoxides, [CHIM.OTHE] Chemical Sciences/Other, Metalloproteins, SOD mimics or mimetics, [CHIM.COOR]Chemical Sciences/Coordination chemistry, X-fluorescence imaging or X-fluorescence microscopy XFM, [CHIM.OTHE]Chemical Sciences/Other
Abstract: International audience; Superoxide dismutases (SODs) are metalloproteins that protect cells against oxidative stress by controlling the concentration of superoxide (O2-) through catalysis of its dismutation. The activity of superoxide dismutases can be mimicked by low-molecular-weight complexes having potential therapeutic applications. This review presents recent strategies for designing efficient SOD mimics, from molecular metal complexes to nanomaterials. Studies of these systems in cells reveal that some SOD mimics, designed to react directly with superoxide, may also indirectly enhance the cellular antioxidant arsenal. Finally, a good understanding of the bioactivity requires information on the cell-penetration, speciation, and subcellular location of the SOD mimics: we will describe recent studies and new techniques that open opportunities for characterizing SOD mimics in biological environments.
Published: 2022

25. In situ solid-state NMR study of antimicrobial peptide interactions with erythrocyte membranes

Author: Kiran Kumar, Mathew Sebastiao, Alexandre A. Arnold, Steve Bourgault, Dror E. Warschawski, Isabelle Marcotte, WARSCHAWSKI, Dror, Université du Québec à Montréal = University of Québec in Montréal (UQAM), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Analyse, Interactions Moléculaires et Cellulaires (LBM-E2), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Chimie Moléculaire de Paris Centre (FR 2769)
Subjects: [SDE] Environmental Sciences, Magnetic Resonance Spectroscopy, New and Notable, [SDV]Life Sciences [q-bio], Erythrocyte Membrane, Lipid Bilayers, Biophysics, Articles, [SDV] Life Sciences [q-bio], [CHIM] Chemical Sciences, [SDE]Environmental Sciences, [CHIM]Chemical Sciences, Antimicrobial Peptides, Antimicrobial Cationic Peptides
Abstract: International audience; Antimicrobial peptides are promising therapeutic agents to mitigate the global rise of antibiotic resistance. They generally act by perturbing the bacterial cell membrane and are thus less likely to induce resistance. Because they are membrane-active molecules, it is critical to verify and understand their potential action toward eukaryotic cells to help design effective and safe drugs. In this work, we studied the interaction of two antimicrobial peptides, aurein 1.2 and caerin 1.1, with red blood cell (RBC) membranes using in situ 31P and 2H solid-state NMR (SS-NMR). We established a protocol to integrate up to 25% of deuterated fatty acids in the membranes of ghosts, which are obtained when hemoglobin is removed from RBCs. Fatty acid incorporation and the integrity of the lipid bilayer were confirmed by SS-NMR and fluorescence confocal microscopy. Leakage assays were performed to assess the lytic power of the antimicrobial peptides. The in situ perturbation of the ghost membranes by aurein 1.2 and caerin 1.1 revealed by 31P and 2H SS-NMR is consistent with membrane perturbation through a carpet mechanism for aurein 1.2, whereas caerin 1.1 acts on RBCs via pore formation. These results are compatible with fluorescence microscopy images of the ghosts. The peptides interact with eukaryotic membranes following similar mechanisms that take place in bacteria, highlighting the importance of hydrophobicity when determining such interactions. Our work bridges model membranes and in vitro studies and provides an analytical toolbox to assess drug toxicity toward eukaryotic cells.
Published: 2022

26. Dynamic Amino Acid Side-Chains Grafting on Folded Peptide Backbone

Author: Benjamin Zagiel, Taleen Peker, Rodrigue Marquant, Guillaume Cazals, Gabrielle Webb, Emeric Miclet, Claudia Bich, Emmanuelle Sachon, Roba Moumné, Sorbonne Université (SU), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), and Moumné, Roba
Subjects: Peptide Library, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, Combinatorial Chemistry Techniques, Proteins, General Chemistry, Amino Acids, Peptides, [CHIM.ORGA] Chemical Sciences/Organic chemistry, Catalysis
Abstract: International audience; An efficient strategy for the synthesis of large libraries of conformationally defined peptides is reported, using dynamic combinatorial chemistry as a tool to graft amino acid side chains on a well-ordered 3D (3-dimension) peptide backbone. Combining rationally designed scaffolds with combinatorial side chains selection represents an alternative method to access peptide libraries for structures that are not genetically encodable. This method would allow a breakthrough for the discovery of protein mimetic for unconventional targets for which little is known.
Published: 2022

27. Redox control of particle deposition from drying drops

Author: Pauline E. Galy, Tiffany Guitton-Spassky, Catherine Sella, Laurent Thouin, Maxime R. Vitale, Damien Baigl, Processus d'Activation Sélective par Transfert d'Energie Uni-électronique ou Radiatif (UMR 8640) (PASTEUR), Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Thouin, Laurent
Subjects: [CHIM.MATE] Chemical Sciences/Material chemistry, Coffee-ring effect, colloids, Particle patterning, ferrocene, General Materials Science, [CHIM.MATE]Chemical Sciences/Material chemistry, surfactants, redox-sensitive, evaporation
Abstract: International audience; The coffee-ring effect (CRE), which denotes the accumulation of non-volatile compounds at the periphery of a pinned sessile drying drop, is a universal and ubiquitous yet complex phenomenon. It is crucial to better understand and control it, either to avoid its various deleterious consequences in many processes requiring homogenous deposition or to exploit it for applications ranging from controlled particle patterning to low-cost diagnostics. Here, we report for the first time the use of a reduction-oxidation (redox) stimulus to cancel the 2 CRE or harness it, leading to a robust and tunable control of particle deposition in drying sessile drops. This is achieved by implementing redox-sensitive ferrocenyl cationic surfactants of different chain lengths in drying drops containing anionic colloids. Varying surfactant hydrophobicity, concentration and redox state allows us not only to control the overall distribution of deposited particles, including the possibility to fully cancel the CRE, but also to modify the microscopic organization of particles inside the deposit. Notably, all other parameters being fixed, this method allows the adjustment of the deposited particle patterns, from polycrystalline rings to uniform disks, as a function of the oxidation rate. We show that the redox control can be achieved either chemically by addition of oxidants, or electrochemically by applying a potential for additive-free and reversible actuation in a closed system. This correlation between the redox state and the particle pattern opens perspective for both redox-programmable particle patterning and original diagnostic applications based on the visual determination of a redox state. It also contributes to clarify the role of surfactant charge and its amphiphilic character in directing particle deposition from drying suspensions.
Published: 2022

28. Hypocrates is a genetically encoded fluorescent biosensor for (pseudo)hypohalous acids and their derivatives

Author: Alexander I. Kostyuk, Maria-Armineh Tossounian, Anastasiya S. Panova, Marion Thauvin, Roman I. Raevskii, Daria Ezeriņa, Khadija Wahni, Inge Van Molle, Anastasia D. Sergeeva, Didier Vertommen, Andrey Yu. Gorokhovatsky, Mikhail S. Baranov, Sophie Vriz, Joris Messens, Dmitry S. Bilan, Vsevolod V. Belousov, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry (IBCh RAS), Russian Academy of Sciences [Moscow] (RAS), Pirogov Russian National Reasearch Medical University Moscow, Vrije Universiteit Brussel (VUB), Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), University College of London [London] (UCL), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Collège Doctoral, Sorbonne Université (SU), Lomonosov Moscow State University (MSU), Université Catholique de Louvain = Catholic University of Louvain (UCL), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), HAL-SU, Gestionnaire, Faculty of Sciences and Bioengineering Sciences, Department of Bio-engineering Sciences, and Structural Biology Brussels
Subjects: Neutrophils, Science, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Biosensing Techniques, Crystallography, X-Ray, General Biochemistry, Genetics and Molecular Biology, Article, Fluorescence imaging, Bacterial Proteins, Phagocytosis, Genes, Reporter, Escherichia coli, Animals, Acute inflammation, Zebrafish, Fluorescent Dyes, Multidisciplinary, Nanocrystallography, Escherichia coli Proteins, Small molecules, General Chemistry, Hydrogen Peroxide, Hypochlorous Acid, [SDV] Life Sciences [q-bio], Luminescent Proteins, Animal Fins, Oxidation-Reduction, Transcription Factors
Abstract: The lack of tools to monitor the dynamics of (pseudo)hypohalous acids in live cells and tissues hinders a better understanding of inflammatory processes. Here we present a fluorescent genetically encoded biosensor, Hypocrates, for the visualization of (pseudo)hypohalous acids and their derivatives. Hypocrates consists of a circularly permuted yellow fluorescent protein integrated into the structure of the transcription repressor NemR from Escherichia coli. We show that Hypocrates is ratiometric, reversible, and responds to its analytes in the 106 M−1s−1 range. Solving the Hypocrates X-ray structure provided insights into its sensing mechanism, allowing determination of the spatial organization in this circularly permuted fluorescent protein-based redox probe. We exemplify its applicability by imaging hypohalous stress in bacteria phagocytosed by primary neutrophils. Finally, we demonstrate that Hypocrates can be utilized in combination with HyPerRed for the simultaneous visualization of (pseudo)hypohalous acids and hydrogen peroxide dynamics in a zebrafish tail fin injury model., There are a lack of tools to study the dynamics of (pseudo)hypohalous acids in live cells. Here the authors report a genetically encoded fluorescent biosensor, Hypocrates, for (pseudo)hypohalous acids and their derivatives which they use in cells and in a zebrafish tail fin injury model.
Published: 2022

29. Lipophilic quinolone derivatives: Synthesis and in vitro antibacterial evaluation

Author: Sadowski, Elodie, Bercot, Beatrice, Chauffour, Aurélie, Gomez, Catherine, Varon, Emmanuelle, Mainardis, Mary, Sougakoff, Wladimir, Mayer, Claudine, Sachon, Emmanuelle, Anquetin, Guillaume, Aubry, Alexandra, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Génomique, bioinformatique et chimie moléculaire (GBCM), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Centre Hospitalier Intercommunal de Créteil (CHIC), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Spectrométrie de masse de Sorbonne Université [IBPS] (MS3U), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Interfaces, Traitements, Organisation et Dynamique des Systèmes (ITODYS (UMR_7086)), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), The work was supported by grants from the order of Malta Grants for Leprosy Research, QUIET Lutech MA077/SL00091 – ref UPMCX13042 from the SATT LUTECH and ANR DETONATOR., ANR-20-CE18-0030,DETONATOR,Décryptage du mode d'action de nouveaux antituberculeux prometteurs(2020), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Centre National de Référence des Mycobactéries et de la Résistance aux Antituberculeux [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Service de Bactériologie et d'Hygiène Hospitalière [CHU Pitié-Salpêtrière], Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Paris (UP), Noel, Anne-Laure, Décryptage du mode d'action de nouveaux antituberculeux prometteurs - - DETONATOR2020 - ANR-20-CE18-0030 - AAPG2020 - VALID, and Centre National de Référence des Mycobactéries et de la Résistance aux Antituberculeux [CHU Pitié-Salpêtrière] (CNR-MyRMA)
Subjects: Dose-Response Relationship, Drug, Molecular Structure, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, ESKAPE, Microbial Sensitivity Tests, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Quinolones, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Neisseria gonorrhoeae, Anti-Bacterial Agents, Antibacterial, Structure-Activity Relationship, Synthesis, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Hydrophobic and Hydrophilic Interactions, Fluoroquinolones
Abstract: International audience; This paper reports on the design of a series of 10 novel lipophilic piperazinyl derivatives of the 1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, their synthesis, their characterisation by 1H, 13C and 19F NMR, IR spectroscopy and HRMS, as well as their biological activity against bacteria of medical interest. Among these derivatives, 2 were as potent as the parent quinolone against Neisseriagonorrhoeae whereas all the compounds displayed lower activity than the parent quinolone against other bacteria of medical interest. Our results showing that the increased lipophilicity was deleterious for antibacterial activity may help to design new quinolone derivatives in the future, especially lipophilic quinolones which have been poorly investigated previously.
Published: 2022

30. Spin relaxation: is there anything new under the Sun?

Author: B. A. Rodin, D. Abergel, Siberian Branch of the Russian Academy of Sciences (SB RAS), Novosibirsk State University (NSU), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Abergel, Daniel
Subjects: Electricity and magnetism, QC501-766, [CHIM] Chemical Sciences, [CHIM]Chemical Sciences
Abstract: Spin relaxation has been at the core of many studies since the early days of nuclear magnetic resonance (NMR) and the underlying theory worked out by its founding fathers. This Bloch–Redfield–Abraham relaxation theory has been recently reinvestigated (Bengs and Levitt, 2020) in the perspective of Lindblad theory of quantum Markovian master equations in order to account for situations where the widely used semi-classical relaxation theory breaks down. In this article, we review the conventional approach of quantum mechanical theory of NMR relaxation and show that, under the usual assumptions, it is equivalent to the Lindblad formulation. We also comment on the debate on semi-classical versus quantum versions of spectral density functions involved in relaxation.
Published: 2022

31. Improvement of Peptidyl Copper Complexes Mimicking Catalase: A Subtle Balance between Thermodynamic Stability and Resistance towards H2O2 Degradation

Author: Yaqine Ben Hadj Hammouda, Koudedja Coulibaly, Alimatou Bathily, Magdalene Teoh Sook Han, Clotilde Policar, Nicolas Delsuc, Delsuc, Nicolas, Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: catalase mimic, di-copper(II) complexes, H2O2 dismutation, metal binding peptide, reactive oxygen species, Chemistry (miscellaneous), Organic Chemistry, Drug Discovery, Molecular Medicine, Pharmaceutical Science, [CHIM.CATA] Chemical Sciences/Catalysis, [CHIM.COOR]Chemical Sciences/Coordination chemistry, [CHIM.CATA]Chemical Sciences/Catalysis, Physical and Theoretical Chemistry, [CHIM.COOR] Chemical Sciences/Coordination chemistry, Analytical Chemistry
Abstract: International audience; Catalase mimics are low molecular weight metal complexes that reproduce the activity of catalase, an antioxidant metalloprotein that participates in the cellular regulation of H2O2 concentration by catalyzing its dismutation. H2O2 is a reactive oxygen species that is vital for the normal functioning of cells. However, its overproduction contributes to oxidative stress, which damages cells. Owing to their biocompatibility, peptidyl complexes are an attractive option for clinical applications to regulate H2O2 by enzyme mimics. We report here the synthesis and characterization of four new peptidyl di-copper complexes bearing two coordinating sequences. Characterization of the complexes showed that, depending on the linker used between the two coordinating sequences, their catalytic activity for H2O2 dismutation, their thermodynamic stability and their resistance to H2O2 degradation are very different, with (CATm2)Cu2 being the most promising catalyst.
Published: 2022

32. Machine Learning Yield Prediction from NiCOlit, a Small-Size Literature Data Set of Nickel Catalyzed C–O Couplings

Author: Jules Schleinitz, Maxime Langevin, Yanis Smail, Benjamin Wehnert, Laurence Grimaud, Rodolphe Vuilleumier, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sanofi [Vitry-sur-Seine], SANOFI Recherche, Processus d'Activation Sélective par Transfert d'Energie Uni-électronique ou Radiatif (UMR 8640) (PASTEUR), Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), and Jules SCHLEINITZ, Jules
Subjects: [CHIM.ORGA]Chemical Sciences/Organic chemistry, [CHIM.GENI] Chemical Sciences/Chemical engineering, [CHIM.CATA] Chemical Sciences/Catalysis, General Chemistry, [CHIM.CATA]Chemical Sciences/Catalysis, [INFO.INFO-LG] Computer Science [cs]/Machine Learning [cs.LG], [CHIM.ORGA] Chemical Sciences/Organic chemistry, Biochemistry, Catalysis, Machine Learning, Colloid and Surface Chemistry, [CHIM.GENI]Chemical Sciences/Chemical engineering, [INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG], Nickel, [CHIM.CHEM] Chemical Sciences/Cheminformatics, [CHIM.CHEM]Chemical Sciences/Cheminformatics
Abstract: International audience; Synthetic yield prediction using machine learning is intensively studied. Previous work focused on two categories of datasets: High-Throughput Experimentation data, as an ideal case study and datasets extracted from proprietary databases, which are known to have a strong reporting bias towards high yields. However, predicting yields using published reaction data remains elusive. To fill the gap, we built a dataset on 1 nickel-catalyzed cross-couplings extracted from organic reaction publications, including scope and optimization information. We demonstrate the importance of including optimization data as a source of failed experiments and emphasize how publication constraints shape the exploration of the chemical space by the synthetic community. While machine learning models still fail to perform out-of-sample predictions, this work shows that adding chemical knowledge enables fair predictions in a low-data regime. Eventually, we hope that this unique public database will foster further improvements of machine learning methods for reaction yield prediction in a more realistic context.
Published: 2022

33. Solid-state NMR study of structural heterogeneity of the apo WT mouse TSPO reconstituted in liposomes

Author: Luminita Duma, Lucile Senicourt, Baptiste Rigaud, Vassilios Papadopoulos, Jean-Jacques Lacapère, Institut de Chimie Moléculaire de Reims - UMR 7312 (ICMR), Université de Reims Champagne-Ardenne (URCA)-Institut de Chimie du CNRS (INC)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des matériaux de Paris-Centre (IMPC), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Southern California (USC), and Duma, Luminita
Subjects: proteoliposomes, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, solid-state NMR, membrane protein, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, General Medicine, Biochemistry, TSPO, conformational mobility
Abstract: International audience; In the last decades, ligand binding to human TSPO has been largely used in clinical neuroimaging, but little is known about the interaction mechanism. Protein conformational mobility plays a key role in the ligand recognition and both, ligand-free and ligand-bound structures, are mandatory for characterizing the molecular binding mechanism. In the absence of crystals for mammalian TSPO, we have exploited solid-state nuclear magnetic resonance (ssNMR) spectroscopy under magic-angle spinning (MAS) to study the apo form of recombinant mouse TSPO (mTSPO) reconstituted in lipids. This environment has been previously described to permit binding of its high-affinity drug ligand PK11195 and appears therefore favourable for the study of molecular dynamics. We have optimized the physical conditions to get the best resolution for MAS ssNMR spectra of the ligand-free mTSPO. We have compared and combined various ssNMR spectra to get dynamical information either for the lipids or for the mTSPO. Partial assignment of residue types suggests few agreements with the published solution NMR assignment of the PK11195-bound mTSPO in DPC detergent. Moreover, we were able to observe some lateral chains of aromatic residues that were not assigned in solution. 13C double-quantum NMR spectroscopy shows remarkable dynamics for ligand-free mTSPO in lipids which may have significant implications on the recognition of the ligand and/or other protein partners.
Published: 2022

34. Introduction à la programmation Python pour la biologie

Author: Fuchs, Patrick F. J., Poulain, Pierre, Poulain, Pierre, Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Cité - UFR Sciences du Vivant [Sciences] (UPCité - UFR SDV), Université Paris Cité (UPCité), Institut Jacques Monod (IJM (UMR_7592)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Université Paris Cité
Subjects: programmation, python, [INFO.INFO-PL]Computer Science [cs]/Programming Languages [cs.PL], biologie, sciences du vivant, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], [INFO.INFO-PL] Computer Science [cs]/Programming Languages [cs.PL]
Abstract: 1. Introduction2. Variables3. Affichage4. Listes5. Boucles et comparaisons6. Tests7. Fichiers8. Modules9. Fonctions10. Plus sur les chaînes de caractères11. Plus sur les listes12. Plus sur les fonctions13. Dictionnaires, tuples et sets14. Création de modules15. Bonnes pratiques en programmation Python16. Expressions régulières17. Quelques modules d'intérêt en bioinformatique18. Jupyter et ses notebooks19. Avoir la classe avec les objets20. Fenêtres graphiques et Tkinter21. Remarques complémentaires22. Mini-projetsAnnexesA. Quelques formats de données rencontrés en biologieB. Installation de Python; Master
Published: 2022

35. Understanding the g-tensors of perchlorotriphenylmethyl and Finland-type trityl radicals

Author: Régis Guillot, Leandro C. Tabares, Paul Demay-Drouhard, H. Y. Vincent Ching, Clotilde Policar, Sun Un, Christophe Decroos, Hélène Bertrand, Yun Li, Laboratoire des biomolécules (LBM UMR 7203), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), RPE Haut Champ des systèmes biologiques (BHFMR), Département Biochimie, Biophysique et Biologie Structurale (B3S), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Laboratoire de Chimie des Processus Biologiques (LCPB), Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC), Université Paris sciences et lettres (PSL), Sorbonne Université (SU), Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), and Decroos, Christophe
Subjects: 010405 organic chemistry, Physics, Radical, Heteroatom, General Physics and Astronomy, Protonation, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, law.invention, Chemistry, chemistry.chemical_compound, Crystallography, Delocalized electron, chemistry, law, [CHIM] Chemical Sciences, [CHIM]Chemical Sciences, Carboxylate, Physical and Theoretical Chemistry, Methylene, Spin (physics), Electron paramagnetic resonance
Abstract: International audience; The 285 GHz EPR spectra of perchlorotriphenylmethyl and tetrathiatriarylmethyl radicals in frozen solution have been accurately measured. The relationship between their molecular structures and their g-tensors has been investigated with the aid of DFT calculations, revealing that the degree of spin density delocalization away from the central methylene carbon is an important determining factor of the g-anisotropy. In particular, the small amount of spin densities on the Cl or S heteroatoms at the 2 and 6 positions with respect to the central carbon have the strongest influence. Furthermore, the amount of spin densities on these heteroatoms and thus the anisotropy can be modulated by the protonation (esterification) state of the carboxylate groups at the 4 position. These results provide unique insights into the g-anisotropy of persistent trityl radicals and how it can be tuned.
Published: 2020

36. Rational De Novo Design of a Cu Metalloenzyme for Superoxide Dismutation

Author: Audrey E. Tolbert, Emilie Mathieu, Vincent L. Pecoraro, James E. Penner-Hahn, Cédric Tard, Clotilde Policar, Karl J. Koebke, Olga Iranzo, Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Laboratoire des biomolécules (LBM UMR 7203), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL), Sorbonne Université (SU), Department of Chemistry, University of Michigan, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Laboratoire de chimie moléculaire (LCM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS-PSL), Chimie Moléculaire de Paris Centre (FR 2769), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and École polytechnique (X)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Stereochemistry, Protein design, chemistry.chemical_element, 010402 general chemistry, 01 natural sciences, Article, Catalysis, Metal, Superoxide dismutase, chemistry.chemical_compound, Metalloproteins, Metalloprotein, [CHIM]Chemical Sciences, Amino Acid Sequence, Enzyme Assays, chemistry.chemical_classification, biology, Protein Stability, Superoxide Dismutase, 010405 organic chemistry, Superoxide, Organic Chemistry, Electron Spin Resonance Spectroscopy, Temperature, Active site, Bioinorganic chemistry, General Chemistry, Copper, 3. Good health, 0104 chemical sciences, chemistry, visual_art, biology.protein, visual_art.visual_art_medium, Thermodynamics, Peptides
Abstract: Superoxide dismutases (SODs) are highly efficient enzymes for superoxide dismutation and the first line of defense against oxidative stress. These metalloproteins contain a redox-active metal ion in their active site (Mn, Cu, Fe, Ni) with a tightly controlled reduction potential found in a close range around the optimal value of 0.36 V versus the normal hydrogen electrode (NHE). Rationally designed proteins with well-defined three-dimensional structures offer new opportunities for obtaining functional SOD mimics. Here, we explore four different copper-binding scaffolds: H3 (His3 ), H4 (His4 ), H2 DH (His3 Asp with two His and one Asp in the same plane) and H3 D (His3 Asp with three His in the same plane) by using the scaffold of the de novo protein GRα3 D. EPR and XAS analysis of the resulting copper complexes demonstrates that they are good CuII -bound structural mimics of Cu-only SODs. Furthermore, all the complexes exhibit SOD activity, though three orders of magnitude slower than the native enzyme, making them the first de novo copper SOD mimics.
Published: 2019

37. Mannose-Coated Fluorescent Lipid Microparticles for Specific Cellular Targeting and Internalization via Glycoreceptor-Induced Phagocytosis

Author: Pascal Matton, Blaise Dumat, Laurent Cattiaux, Léa Pinon, Lorraine Montel, Jean-Maurice Mallet, Jacques Fattaccioli, Dumat, Blaise, Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Processus d'Activation Sélective par Transfert d'Energie Uni-électronique ou Radiatif (UMR 8640) (PASTEUR), Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre-Gilles de Gennes pour la Microfluidique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Physique des Solides (LPS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)
Subjects: fluorescent glycolipids, Phagocytosis, media_common.quotation_subject, Biomedical Engineering, Mannose, Cellular targeting, 010402 general chemistry, 01 natural sciences, Biomaterials, oil-in-water emulsion droplets, carbohydrateslectins interactions, 03 medical and health sciences, chemistry.chemical_compound, Cell surface receptor, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, Internalization, mannose receptor, 030304 developmental biology, media_common, 0303 health sciences, biology, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Biochemistry (medical), phagocytosis, Lectin, General Chemistry, [CHIM.ORGA] Chemical Sciences/Organic chemistry, Fluorescence, 0104 chemical sciences, Cell biology, [SDV.IB.BIO] Life Sciences [q-bio]/Bioengineering/Biomaterials, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, [CHIM.THEO] Chemical Sciences/Theoretical and/or physical chemistry, chemistry, biology.protein, Mannose receptor
Abstract: International audience; In this work we report on the development of mannose-coated fluorescent lipid microparticles to study the role of C-type lectin membrane receptor in phagocytosis. The micrometric droplets of soybean oil in water emulsion were functionalized with a tailor-made fluorescent mannolipid. The amphiphilic ligand was built from a mannose unit, a lipid C11 spacer and a naphthalimide fluorophore. The droplets functionalization was monitored by fluorescence microscopy as well as the interaction with concanavalin A which was used as a model lectin in vitro. The use of a monovalent ligand on the surface of emulsion droplets yielded particles with an affinity approximately 40 times higher than that of free mannose. In cellulo, the coated droplets were shown to be specifically internalized by macrophages in a receptor-dependent phagocytic pathway. The naked droplets on the other hand display very little internalization due to their low immunogenicity. This work thus brings evidence that C-type lectin membrane receptors may act as phagocytic receptors. The droplets functionalization with the tailored amphiphilic fluorescent ligand and the droplets functionalization also provides insights into the development of organic fluorescent particles that may prove useful for developing targeted imaging and delivery tools.
Published: 2019

38. Effects of Microwave Gating on Nuclear Spin Echoes in Dynamic Nuclear Polarization

Author: David Guarin, Diego Carnevale, Mathieu Baudin, Philippe Pelupessy, Daniel Abergel, Geoffrey Bodenhausen, Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Gestionnaire, Hal Sorbonne Université
Subjects: Dynamic Nuclear Polarization, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Microwave gating, Quadrupolar echoes, Physics::Medical Physics, Surge of spin echoes, Electron spin relaxation, General Materials Science, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Physical and Theoretical Chemistry, Dipolar echoes, Transverse relaxation, Slump of spin echoes
Abstract: International audience; Dipolar or quadrupolar echoes allow one to observe undistorted powder patterns, in contrast to simple Fourier transformations of free induction decays (FIDs). In this work, the build-up of proton polarization due to dynamic nuclear polarization (DNP) is monitored by observing echoes rather than FIDs. When the microwave irradiation is interrupted during the build-up of DNP, the electrons relax back to their Boltzmann distribution at high fields (B0 = 6.7 T) and low temperatures 1.2 < Tsample < 4.0 K, so that dipolar flip-flop-flip terms involving two electrons and one proton become largely ineffective as a mechanism of proton decoherence. This leads to a prolongation of the nuclear coherence lifetime T2'(1 H). The increase in T2'(1 H) leads to transient surges of the amplitudes of spin echoes. Conversely, transient slumps of spin echoes are observed when the microwave irradiation is switched back on, due to a shortening of nuclear coherence lifetimes.
Published: 2021

39. FKBP52 in Neuronal Signaling and Neurodegenerative Diseases: A Microtubule Story

Author: Béatrice Chambraud, Cillian Byrne, Geri Meduri, Etienne Emile Baulieu, Julien Giustiniani, Université Paris-Saclay, Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Gestionnaire, HAL Sorbonne Université 5
Subjects: QH301-705.5, Microtubules, Catalysis, Inorganic Chemistry, Tacrolimus Binding Proteins, Protein Aggregates, synuclein, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Physical and Theoretical Chemistry, Biology (General), Molecular Biology, QD1-999, Spectroscopy, Neurons, Organic Chemistry, Neurodegenerative Diseases, General Medicine, Computer Science Applications, Parkinson disease, Chemistry, FKBP52, Tau, Alzheimer disease, microtubule, Signal Transduction
Abstract: International audience; The FK506-binding protein 52 (FKBP52) belongs to a large family of ubiquitously expressed and highly conserved proteins (FKBPs) that share an FKBP domain and possess Peptidyl-Prolyl Isomerase (PPIase) activity. PPIase activity catalyzes the isomerization of Peptidyl-Prolyl bonds and therefore influences target protein folding and function. FKBP52 is particularly abundant in the nervous system and is partially associated with the microtubule network in different cell types suggesting its implication in microtubule function. Various studies have focused on FKBP52, highlighting its importance in several neuronal microtubule-dependent signaling pathways and its possible implication in neurodegenerative diseases such as tauopathies (i.e., Alzheimer disease) and alpha-synucleinopathies (i.e., Parkinson disease). This review summarizes our current understanding of FKBP52 actions in the microtubule environment, its implication in neuronal signaling and function, its interactions with other members of the FKBPs family and its involvement in neurodegenerative disease.
Published: 2021

40. Peptide mimics of glycosaminoglycans : synthesis, structures and biological activities

Author: Marquant, Rodrigue, Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université, Jean-Maurice Mallet, Solange Lavielle, and STAR, ABES
Subjects: [CHIM.ORGA]Chemical Sciences/Organic chemistry, Glycosaminoglycanes, Mimics, Homeodomain, Mimes, Sulfopeptides, [CHIM.ORGA] Chemical Sciences/Organic chemistry, RMN, Biacore, Homéodomaine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Glycosaminoglycans, Otx2
Abstract: Glycosaminoglycans (GAGs) are linear polysaccharides, more or less sulfated, present on the surface of cells and in the extracellular matrix. They interact with a large number of proteins (cytokines, growth factors, enzymes, etc.) and are involved in various physiological and pathological processes. As part of my thesis work, we designed and synthesized GAGs mimetic molecules: anionic peptides of 12 to 24 amino acids, carrying repeated motifs (EC'AC ')n and exhibiting the characteristic functions of natural GAGs, namely the acid functions, provided by glutamic acid, and sulfonic functions, obtained by oxidation of cysteines. A first generation of these sulfopeptides was studied, at the Collège de France, as inhibitors of the interaction of a homeodomain protein (Otx2) with the network of GAGs present around a target cell type of this protein. The peptide comprising six "EC'AC" motifs has shown very promising in vivo activity. A structural study by NMR was then carried out to analyze the interactions of these sulfopeptides with the Otx2 protein produced with a double 13C, 15N labeling. This study confirmed that the interaction takes place at the GAG binding domain of the protein. This interaction also affects the homeodomain helix 3, which is responsible for the internalization of Otx2 into cells. Finally, we completed this structural study with a Biacore-type approach, to develop a strategy for faster analysis of the activity of our analogues and allow us to develop an efficient structure-activity study., Les Glycosaminoglycanes (GAGs) sont des polysaccharides linéaires, plus ou moins sulfatés, présents à la surface des cellules et dans la matrice extracellulaire. Ils interagissent avec un grand nombre de protéines (cytokines, facteurs de croissance, enzymes ...) et sont impliqués dans divers processus physiologiques et pathologiques. Dans le cadre de mon travail de thèse, nous avons conçu et synthétisé des molécules mimes de GAGs : des peptides anioniques de 12 à 24 acides aminés, portant des motifs répétés de type (EC’AC’)n et présentant les fonctions caractéristiques des GAGs naturels, à savoir les fonctions acides, apportées par l’acide Glutamique, et sulfoniques, obtenues par oxydation des Cystéines. Une première génération de ces sulfopeptides a été étudiée, au Collège de France, comme inhibiteurs de l’interaction d’une protéine à homéodomaine (Otx2) avec le réseau de GAGs présents autour d’un type cellulaire cible de cette protéine. Le peptide comportant six motifs « EC’AC’» a montré une activité in vivo très prometteuse. Une étude structurale par RMN a ensuite été réalisée pour analyser les interactions de ces sulfopeptides avec la protéine Otx2 produite avec un double marquage 13C, 15N. Cette étude a confirmé que l’interaction se faisait au niveau du domaine de liaison aux GAGs de la protéine. Cette interaction affecte aussi l’hélice 3 de l’homéodomaine, à l’origine de l’internalisation d’Otx2 dans les cellules. Enfin nous avons complété cette étude structurale par une approche de type Biacore, pour développer une stratégie d’analyse plus rapide de l’activité de nos analogues et nous permettre de développer une étude structure-activité efficace.
Published: 2021

41. Cellular Detection of a Mitochondria Targeted Brominated Vinyl Triphenylamine Optical Probe (TP-Br) by X-Ray Fluorescence Microscopy

Author: Sounderya Nagarajan, Florent Poyer, Laura Fourmois, Delphine Naud‐Martin, Kadda Medjoubi, Andrea Somogyi, Gabrielle Schanne, Lucas Henry, Nicolas Delsuc, Clotilde Policar, Helene C. Bertrand, Florence Mahuteau‐Betzer, Chimie et modélisation pour la biologie du cancer (CMBC), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Mahuteau-Betzer, Florence
Subjects: Photons, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Microscopy, Fluorescence, [CHIM.ORGA]Chemical Sciences/Organic chemistry, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, X-Rays, Organic Chemistry, Optical Imaging, General Chemistry, [CHIM.ORGA] Chemical Sciences/Organic chemistry, Catalysis, Fluorescent Dyes, Mitochondria
Abstract: International audience; Triphenylamine (TP) derivatives such as two-branch cationic vinylbenzimidazolium triphenylamine TP−2Bzim are promising turn-on fluorescent probes suitable for two-photon imaging, labelling mitochondria in live cells. Here, we designed two TP−2Bzim derivatives as bimodal probes suitable for X-ray fluorescence imaging. The conjugation of the TP core with a rhenium tricarbonyl moiety in the TP−RePyta probe altered the localisation in live cells from mitochondria to lysosomes. The introduction of bromine on the TP core generated the TP−Br probe retaining good photophysical properties and mitochondria labelling in live cells. The influence of calcium channels in the uptake of TP−Br was studied. Synchrotron Radiation X-ray Fluorescence (SXRF) imaging of bromine enabled the detection of TP−Br and suggested a negligible presence of the probe in an unbound state in the incubated cells, a crucial point in the development of these probes. This study paves the way towards the development of TP probes as specific organelle stainers suitable for SXRF imaging
Published: 2021

42. Identification and Quantification of Glycans in Whole Cells: Architecture of Microalgal Polysaccharides Described by Solid-State Nuclear Magnetic Resonance

Author: Tuo Wang, Artur Muszyński, Alexandre A. Arnold, Malitha C. Dickwella Widanage, Parastoo Azadi, Dror E. Warschawski, Isabelle Marcotte, Alexandre Poulhazan, Université du Québec à Montréal = University of Québec in Montréal (UQAM), Louisiana State University (LSU), University of Georgia [USA], Laboratoire des biomolécules (LBM UMR 7203), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), EADS Innovation Works [Toulouse], EADS - European Aeronautic Defense and Space, Département de Chimie [Montréal], Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Gestionnaire, HAL Sorbonne Université 5
Subjects: [CHIM.POLY] Chemical Sciences/Polymers, Glycan, glycolipids, [CHIM.ANAL] Chemical Sciences/Analytical chemistry, carbohydrates, Chlorella, 010402 general chemistry, Polysaccharide, 01 natural sciences, Biochemistry, Catalysis, Article, Cell wall, 03 medical and health sciences, chemistry.chemical_compound, Colloid and Surface Chemistry, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Polysaccharides, Bioproducts, Carbohydrate Conformation, Microalgae, [CHIM]Chemical Sciences, Glycosyl, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Nuclear Magnetic Resonance, Biomolecular, 030304 developmental biology, mass spectrometry, chemistry.chemical_classification, 0303 health sciences, biology, Chemistry, starch, General Chemistry, biology.organism_classification, Xylan, 0104 chemical sciences, [CHIM.POLY]Chemical Sciences/Polymers, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Solid-state nuclear magnetic resonance, biology.protein, solid-state NMR, cell wall
Abstract: International audience; Microalgae are photosynthetic organisms widely distributed in nature and serve as a sustainable source of bioproducts. Their carbohydrate components are also promising candidates for bioenergy production and bioremediation, but the structural characterization of these heterogeneous polymers in cells remains a formidable problem. Here we present a widely applicable protocol for identifying and quantifying the glycan content using magic-angle-spinning (MAS) solid-state NMR (ssNMR) spectroscopy, with validation from glycosyl linkage and composition analysis deduced from mass-spectrometry (MS). Two-dimensional 13 C− 13 C correlation ssNMR spectra of a uniformly 13 C-labeled green microalga Parachlorella beijerinckii reveal that starch is the most abundant polysaccharide in a naturally cellulose-deficient strain, and this polymer adopts a well-organized and highly rigid structure in the cell. Some xyloses are present in both the mobile and rigid domains of the cell wall, with their chemical shifts partially aligned with the flat-ribbon 2-fold xylan identified in plants. Surprisingly, most other carbohydrates are largely mobile, regardless of their distribution in glycolipids or cell walls. These structural insights correlate with the high digestibility of this cellulose-deficient strain, and the in-cell ssNMR methods will facilitate the investigations of other economically important algae species.
Published: 2021

43. Introducing the Chiral Constrained α-Trifluoromethylalanine in Aib Foldamers to Control, Quantify and Assign the Helical Screw-Sense

Author: Lizeth Bodero, Karine Guitot, Nathalie Lensen, Olivier Lequin, Thierry Brigaud, Sandrine Ongeri, Grégory Chaume, Biomolécules : Conception, Isolement, Synthèse (BioCIS), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CY Cergy Paris Université (CY), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Brigaud, Thierry
Subjects: Models, Molecular, Alanine, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Circular Dichroism, Organic Chemistry, Bone Screws, [CHIM.CRIS]Chemical Sciences/Cristallography, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, General Chemistry, [CHIM.CRIS] Chemical Sciences/Cristallography, Catalysis, Protein Structure, Secondary
Abstract: International audience; Oligomers of α-aminoisobutyric acid (Aib) are achiral peptides that adopt 310 helical structures with equal population of left- and right-handed conformers. The screw-sense preference of the helical chain may be controlled by a single chiral residue located at one terminus. 1H and 19F NMR, X-ray crystallography and circular dichroism studies on new Aib oligomers show that the incorporation of a chiral quaternary α-trifluoromethylalanine at their N-terminus induces a reversal of the screw-sense preference of the 310-helix compared to that of a non-fluorinated analogue having an l-α-methyl valine residue. This work demonstrates that, among the many particular properties of introducing a trifluoromethyl group into foldamers, its stereo-electronic properties are of major interest to control the helical screw sense. Its use as an easy-to-handle 19F NMR probe to reliably determine both the magnitude of the screw-sense preference and its sign assignment is also of remarkable interest.
Published: 2021

44. Impact of anti-tumor necrosis factor agents on the risk of colorectal cancer in patients with ulcerative colitis: nationwide French cohort study Short title: Colorectal cancer and anti-TNF in UC

Author: Charkaoui, Maeva, Hajage, David, Tubach, Florence, Laurent, Beaugerie, Kirchgesner, Julien, Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Département de santé publique, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Laboratoire des biomolécules (LBM UMR 7203), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Département de santé publique [CHU Pitié-Salpêtrière], CHU Saint-Antoine [AP-HP], Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Gestionnaire, HAL Sorbonne Université 5
Subjects: inflammatory bowel disease, colorectal cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, ulcerative colitis
Abstract: International audience; Background and Aims: Patients with ulcerative colitis (UC) are at increased risk of colorectal cancer. Anti-tumor necrosis factor agents (anti-TNF) aim to reduce chronic colonic inflammation and may lower the risk of colorectal cancer (CRC), but the impact of anti-TNF exposure has not yet been assessed in population-based cohort studies. The aim of this nationwide study was to assess the risk of CRC in patients with UC exposed to anti-TNF. Methods: Based on the French health insurance database, patients aged 18 years or older with a diagnosis of UC, previously exposed to or initiating immunosuppressive treatment were followed from 1 January 2009 until 31 December 2018. The risk of CRC associated with anti-TNF exposure was assessed using marginal structural Cox proportional hazard models adjusting for baseline and time-varying comorbidities including primary sclerosing cholangitis, UC disease activity, colonoscopic surveillance, and other medications. Results: Among 32,403 patients with UC, 15,542 (48.0%) were exposed to anti-TNF. During a median follow-up of 6.1 years (198,249 person-years), 246 incident CRC occurred (incidence rate per 1000 person-years, 1.24; 95% CI, 1.10-1.41). While the risk of CRC associated with anti-TNF exposure was not decreased in the overall group of patients with UC (HR, 0.85; 95% CI, 0.58-1.26), anti-TNF exposure was associated with a decreased risk of CRC in patients with long-standing colitis (disease duration ≥ 10 years) (HR, 0.41; 95% CI, 0.20-0.86). Conclusions: In a nationwide cohort of patients with UC, anti-TNF exposure was associated with a decreased risk of CRC in patients with long-standing colitis.
Published: 2021

45. Antitumor Activity and Mechanism of Action of Hormonotoxin, an LHRH Analog Conjugated to Dermaseptin-B2, a Multifunctional Antimicrobial Peptide

Author: Couty, Mickael, Dusaud, Marie, Miro-Padovani, Mickael, Zhang, Liuhui, Zadigue, Patricia, Zargarian, Loussiné, Lequin, Olivier, Taille, Alexandre de la, Delbe, Jean, Hamma-Kourbali, Yamina, Amiche, Mohamed, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire de biologie et pharmacologie appliquée (LBPA), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), Laboratoire des biomolécules (LBM UMR 7203), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Biosynthèse des Signaux Peptidiques [IBPS] (IBPS-BIOSIPE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Amiche, Mohamed, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: frog skin peptides, Cell Survival, QH301-705.5, antimicrobial peptide (AMP), Mice, Nude, Antineoplastic Agents, Apoptosis, Phyllomedusa bicolor, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Amphibian Proteins, Article, LHRH, Gonadotropin-Releasing Hormone, Mice, [SDV.CAN] Life Sciences [q-bio]/Cancer, therapeutic peptides, Cell Movement, Cell Line, Tumor, Neoplasms, Animals, Humans, Immunologic Factors, anticancer drug, Amino Acid Sequence, Biology (General), QD1-999, dermaseptin, prostate cancer, Xenograft Model Antitumor Assays, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Anti-Bacterial Agents, Chemistry, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Antimicrobial Peptides, Antimicrobial Cationic Peptides
Abstract: International audience; Prostate cancer is the most common cancer in men. For patients with advanced or metastatic prostate cancer, available treatments can slow down its progression but cannot cure it. The development of innovative drugs resulting from the exploration of biodiversity could open new therapeutic alternatives. Dermaseptin-B2, a natural multifunctional antimicrobial peptide isolated from Amazonian frog skin, has been reported to possess antitumor activity. To improve its pharmacological properties and to decrease its peripheral toxicity and lethality we developed a hormonotoxin molecule composed of dermaseptin-B2 combined with d-Lys6-LHRH to target the LHRH receptor. This hormonotoxin has a significant antiproliferative effect on the PC3 tumor cell line, with an IC50 value close to that of dermaseptin-B2. Its antitumor activity has been confirmed in vivo in a xenograft mouse model with PC3 tumors and appears to be better tolerated than dermaseptin-B2. Biophysical experiments showed that the addition of LHRH to dermaseptin-B2 did not alter its secondary structure or biological activity. The combination of different experimental approaches indicated that this hormonotoxin induces cell death by an apoptotic mechanism instead of necrosis, as observed for dermaseptin-B2. These results could explain the lower toxicity observed for this hormonotoxin compared to dermaseptin-B2 and may represent a promising targeting approach for cancer therapyY
Published: 2021

46. A New Manganese Superoxide Dismutase Mimetic Improves Oxaliplatin-Induced Neuropathy and Global Tolerance in Mice

Author: Caroline Prieux-Klotz, Henri Chédotal, Martha Zoumpoulaki, Sandrine Chouzenoux, Charlotte Chêne, Alvaro Lopez-Sanchez, Marine Thomas, Priya Ranjan Sahoo, Clotilde Policar, Frédéric Batteux, Hélène C. Bertrand, Carole Nicco, Romain Coriat, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL), Sorbonne Université (SU), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Policar, Clotilde
Subjects: [CHIM.INOR] Chemical Sciences/Inorganic chemistry, colorectal cancer, Antineoplastic Agents, [CHIM.INOR]Chemical Sciences/Inorganic chemistry, Catalysis, superoxide dismutase mimetic, Inorganic Chemistry, Mice, Pt(IV) prodrugs, Superoxides, Animals, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, Mice, Inbred BALB C, oxaliplatin-induced peripheral neuropathy, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Superoxide Dismutase, Organic Chemistry, Peripheral Nervous System Diseases, Hydrogen Peroxide, General Medicine, [CHIM.COOR] Chemical Sciences/Coordination chemistry, [CHIM.ORGA] Chemical Sciences/Organic chemistry, Computer Science Applications, Oxaliplatin, [CHIM.OTHE] Chemical Sciences/Other, [CHIM.OTHE]Chemical Sciences/Other, Reactive Oxygen Species
Abstract: International audience; Reactive oxygen species (ROS) are produced by every aerobic cell during mitochondrial oxidative metabolism as well as in cellular response to xenobiotics, cytokines, and bacterial invasion. Superoxide Dismutases (SOD) are antioxidant proteins that convert superoxide anions (O 2 •−) to hydrogen peroxide (H 2 O 2) and dioxygen. Using the differential in the level of oxidative stress between normal and cancer cells, SOD mimetics can show an antitumoral effect and prevent oxaliplatininduced peripheral neuropathy. New Pt(IV) conjugate prodrugs (OxPt-x-Mn1C1A (x = 1, 1-OH, 2)), combining oxaliplatin and a Mn SOD mimic (MnSODm Mn1C1A) with a covalent link, were designed. Their stability in buffer and in the presence of sodium ascorbate was studied. In vitro, their antitumoral activity was assessed by the viability and ROS production of tumor cell lines (CT16, HCT 116, KC) and fibroblasts (primary culture and NIH 3T3). In vivo, a murine model of colorectal cancer was created with subcutaneous injection of CT26 cells in Balb/c mice. Tumor size and volume were measured weekly in four groups: vehicle, oxaliplatin, and oxaliplatin associated with MnSODm Mn1C1A and the bis-conjugate OxPt-2-Mn1C1A. Oxaliplatin-induced peripheral neuropathy (OIPN) was assessed using a Von Frey test reflecting chronic hypoalgesia. Tolerance to treatment was assessed with a clinical score including four items: weight loss, weariness, alopecia, and diarrhea. In vitro, Mn1C1A associated with oxaliplatin and Pt(IV) conjugates treatment induced significantly higher production of H 2 O 2 in all cell lines and showed a significant improvement of the antitumoral efficacy compared to oxaliplatin alone. In vivo, the association of Mn1C1A to oxaliplatin did not decrease its antitumoral activity, while OxPt-2-Mn1C1A had lower antitumoral activity than oxaliplatin alone. Mn1C1A associated with oxaliplatin significantly decreased OIPN and also improved global clinical tolerance of oxaliplatin. A neuroprotective effect was observed, associated with a significantly improved tolerance to oxaliplatin without impairing its antitumoral activity.
Published: 2022

47. A Conjugate between Lqh-8/6, a Natural Peptide Analogue of Chlorotoxin, and Doxorubicin Efficiently Induces Glioma Cell Death

Author: Lucie Dardevet, Feten Najlaoui, Sonia Aroui, Mayeul Collot, Céline Tisseyre, Michael W. Pennington, Jean-Maurice Mallet, Michel De Waard, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP), Université de Monastir - University of Monastir (UM), Laboratoire de Bioimagerie et Pathologies (LBP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université Grenoble Alpes (UGA), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Collot, Mayeul
Subjects: Lqh-8/6, chlorotoxin, glioma cells, apoptosis, doxorubicin, conjugation, click chemistry, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Medicine (miscellaneous), [SDV.CAN]Life Sciences [q-bio]/Cancer, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, General Biochemistry, Genetics and Molecular Biology, [SDV.CAN] Life Sciences [q-bio]/Cancer
Abstract: International audience; Natural peptides isolated from animal venoms generally target cell surface receptors with high affinity and selectivity. On many occasions, some of these receptors are over-expressed in cancer cells. Herein, we identified Lqh-8/6 as a natural peptide analog of chlorotoxin, a proven and useful compound for the diagnosis and treatment of glioma. Lqh-8/6 and two other natural analogues were chemically synthesized for the first time and evaluated for their ability to label, detect and prevent glioma growth in vitro. We demonstrate that a biotinylated version of Lqh-8/6 allows both the labeling of glioma cell lines and the detection of glioma in brain sections of glioma allograft Fisher rats. Lqh-8/6 has intrinsic anti-invasive properties but is non-toxic to glioma cells. To confer anti-tumor properties to Lqh-8/6, we chemically coupled doxorubicin to the glioma-targeting peptide using click chemistry. To this end, we successfully chemically synthesized Lqh-8/6-azide and doxorubicin-alkyne without impairing the toxic nature of doxorubicin. The toxin-drug conjugate efficiently promotes the apoptosis of glioma cells in vitro. This example contributes to the concept that animal venom peptides constitute exquisite warheads for delivering toxic chemical conjugates, a parallel to the popular concept of antibody-drug conjugates for the treatment of cancer.
Published: 2022

48. Impact of milk polar lipid supplementation on postprandial bile acid composition

Author: Le Barz, Mélanie, Vors, Cecile, L, Humbert, Gauliard, Emilie, Gaborit, Paul, Lambert Porcheron, Stéphanie, Ouchchane, Lemlih, Vidal, Hubert, Malpuech Brugère, Corinne, Rainteau, Dominique, Michalski, Marie-Caroline, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratoire des biomolécules (LBM UMR 7203), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), ACTALIA [Villers-Bocage], Université Clermont Auvergne (UCA), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), École normale supérieure de Lyon (ENS de Lyon)-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Actalia [Saint-Lô], Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), and BOGUAIS, SANDRINE
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract: International audience; Bile acids (BA) are the end products of cholesterol catabolism and may act as signalling molecules and metabolic regulators of energy homeostasis. Disorders in BA metabolism can lead to liver and cardiovascular diseases. In a 4-week double-blind RCT, we demonstrated that the daily consumption of a cream cheese enriched with 3 or 5g of milk polar lipids (PL) improved lipid metabolism by reducing hypercholesterolemia in overweight postmenopausal women. Postprandial (pp) metabolic explorations (0-480 min) were performed before and after the intervention, including a standardized high fat-high sucrose breakfast at fasting and a standardized lunch containing the test cream cheese at 240min. We aimed to determine the effect of milk PL on circulating BA in the fasting and pp state. Before intervention, serum concentration of total fasting BA in the 3 groups was within physiological concentrations (
Published: 2021

49. Spin relaxation: under the sun, anything new?

Author: Bogdan A. Rodin, Daniel Abergel, nternational Tomography Center (ITC), Novosibirsk State University, Pirogova St. 2, Novosibirsk 630090, Russia, Novosibirsk State University (NSU), Laboratoire des biomolécules (LBM UMR 7203), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Abergel, Daniel, Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Physics, [PHYS]Physics [physics], Quantum mechanics, Relaxation (NMR), Master equation, Core (graph theory), [CHIM] Chemical Sciences, Spectral density, [CHIM]Chemical Sciences, Spin relaxation, Quantum, [PHYS] Physics [physics]
Abstract: Spin relaxation has been at the core of many studies since the early days of NMR, and the undelying theory worked out by its founding fathers. However, this theory has been recently questioned (Bengs and Levitt (2020)) in the light of Linblad theory of quantum Markovian master equations. In this article, we review the conventional approach of quantum mechanical theory of NMR relaxation and show that under the usual assumptions, it is equivalent to the Linblad formulation. We also comment on the debate over semi-classical versus quantum versions of spectral density functions involved in relaxation.
Published: 2021

50. Inverse Conformational Selection in Lipid–Protein Binding

Author: Matti Javanainen, Salla I. Virtanen, Fernando Favela-Rosales, Chris Papadopoulos, Antonio Peón, Amélie Bacle, Anne M. Kiirikki, Patrick F.J. Fuchs, O. H. Samuli Ollila, Pavel Buslaev, Ángel Piñeiro, Rebeca García-Fandiño, Paula Milán Rodríguez, Tiago Mendes Ferreira, Markus S. Miettinen, Jesper J. Madsen, Josef Melcr, Ivan Gushchin, Thomas J. Piggot, Lipotoxicity and Channelopathies - ConicMeds (LitCh), Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Nanoscience Center [Jyväskylä Univ] (NSC@JYU), University of Jyväskylä (JYU), Moscow Institute of Physics and Technology [Moscow] (MIPT), Centro de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS ), Universidade de Santiago de Compostela [Spain] (USC ), Universidade do Porto = University of Porto, Tecnológico Nacional de México (TecNM), Martin-Luther-University Halle-Wittenberg, Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UFR Sciences du Vivant [Sciences] - Université Paris Cité (UFR SDV UPCité), Université Paris Cité (UPCité), Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB / CAS), Czech Academy of Sciences [Prague] (CAS), HiLIFE - Institute of Biotechnology [Helsinki] (BI), Helsinki Institute of Life Science (HiLIFE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, University of Chicago, University of South Florida [Tampa] (USF), Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen [Groningen], Max Planck Institute of Colloids and Interfaces, Max-Planck-Gesellschaft, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), University of Southampton, Molecular Dynamics, Institute of Biotechnology, Biophysical chemistry, Gestionnaire, Hal Sorbonne Université, Université Paris Cité - UFR Sciences du Vivant [Sciences] (UPCité - UFR SDV), Université de Poitiers-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Universidade do Porto, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Paris - UFR Sciences du Vivant [Sciences] (UP - UFR SDV), Université de Paris (UP), University of Helsinki-University of Helsinki, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: DYNAMICS, ELECTRIC CHARGE, BILAYERS, PHOSPHATIDYLCHOLINE HEADGROUP, Membrane lipids, DEUTERIUM, Plasma protein binding, Molecular Dynamics Simulation, lipidit, 010402 general chemistry, 01 natural sciences, Biochemistry, biomolekyylit, Catalysis, 03 medical and health sciences, Molecular dynamics, kemialliset sidokset, Colloid and Surface Chemistry, Protein structure, PHOSPHOLIPID-BINDING, MAGNETIC-RESONANCE, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, SEGMENTAL ORDER, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Conformational ensembles, Nuclear Magnetic Resonance, Biomolecular, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Chemistry, Biomolecule, MEMBRANE-LIPIDS, Proteins, Phosphatidylglycerols, General Chemistry, computer.file_format, Protein Data Bank, Lipids, 0104 chemical sciences, Biophysics, Phospholipid Binding, Phosphatidylcholines, MAS NMR, 1182 Biochemistry, cell and molecular biology, lipids (amino acids, peptides, and proteins), proteiinit, computer, Protein Binding
Abstract: International audience; Interest in lipid interactions with proteins and other biomolecules is emerging not only in fundamental biochemistry but also in the field of nanobiotechnology where lipids are commonly used, for example, in carriers of mRNA vaccines. The outward-facing components of cellular membranes and lipid nanoparticles, the lipid headgroups, regulate membrane interactions with approaching substances, such as proteins, drugs, RNA, or viruses. Because lipid headgroup conformational ensembles have not been experimentally determined in physiologically relevant conditions, an essential question about their interactions with other biomolecules remains unanswered: Do headgroups exchange between a few rigid structures, or fluctuate freely across a practically continuous spectrum of conformations? Here, we combine solid-state NMR experiments and molecular dynamics simulations from the NMRlipids Project to resolve the conformational ensembles of headgroups of four key lipid types in various biologically relevant conditions. We find that lipid headgroups sample a wide range of overlapping conformations in both neutral and charged cellular membranes, and that differences in the headgroup chemistry manifest only in probability distributions of conformations. Furthermore, the analysis of 894 protein-bound lipid structures from the Protein Data Bank suggests that lipids can bind to proteins in a wide range of conformations, which are not limited by the headgroup chemistry. We propose that lipids can select a suitable headgroup conformation from the wide range available to them to fit the various binding sites in proteins. The proposed inverse conformational selection model will extend also to lipid binding to targets other than proteins, such as drugs, RNA, and viruses.
Published: 2021

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