Author: "Isabelle Correia" - Searchworks@Jio Institute Digital Library Search Results

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33 results on '"Isabelle Correia"'

1. In vivo characterization of the activities of novel cyclodipeptide oxidases: new tools for increasing chemical diversity of bioproduced 2,5-diketopiperazines in Escherichia coli

Author: Fabien Le Chevalier, Isabelle Correia, Lucrèce Matheron, Morgan Babin, Mireille Moutiez, Nicolas Canu, Muriel Gondry, Olivier Lequin, and Pascal Belin
Subjects: Synthetic biology, Combinatorial biosynthesis, Natural products, 2,5-diketopiperazine, Cyclodipeptide synthase, Cyclodipeptide oxidase, Microbiology, QR1-502
Abstract: Abstract Background Cyclodipeptide oxidases (CDOs) are enzymes involved in the biosynthesis of 2,5-diketopiperazines, a class of naturally occurring compounds with a large range of pharmaceutical activities. CDOs belong to cyclodipeptide synthase (CDPS)-dependent pathways, in which they play an early role in the chemical diversification of cyclodipeptides by introducing Cα-Cβ dehydrogenations. Although the activities of more than 100 CDPSs have been determined, the activities of only a few CDOs have been characterized. Furthermore, the assessment of the CDO activities on chemically-synthesized cyclodipeptides has shown these enzymes to be relatively promiscuous, making them interesting tools for cyclodipeptide chemical diversification. The purpose of this study is to provide the first completely microbial toolkit for the efficient bioproduction of a variety of dehydrogenated 2,5-diketopiperazines. Results We mined genomes for CDOs encoded in biosynthetic gene clusters of CDPS-dependent pathways and selected several for characterization. We co-expressed each with their associated CDPS in the pathway using Escherichia coli as a chassis and showed that the cyclodipeptides and the dehydrogenated derivatives were produced in the culture supernatants. We determined the biological activities of the six novel CDOs by solving the chemical structures of the biologically produced dehydrogenated cyclodipeptides. Then, we assessed the six novel CDOs plus two previously characterized CDOs in combinatorial engineering experiments in E. coli. We co-expressed each of the eight CDOs with each of 18 CDPSs selected for the diversity of cyclodipeptides they synthesize. We detected more than 50 dehydrogenated cyclodipeptides and determined the best CDPS/CDO combinations to optimize the production of 23. Conclusions Our study establishes the usefulness of CDPS and CDO for the bioproduction of dehydrogenated cyclodipeptides. It constitutes the first step toward the bioproduction of more complex and diverse 2,5-diketopiperazines.
Published: 2020
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2. The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

Author: Yaochun Xu, Isabelle Correia, Tap Ha-Duong, Nadjib Kihal, Jean-Louis Soulier, Julia Kaffy, Benoît Crousse, Olivier Lequin, and Sandrine Ongeri
Subjects: aggregation, beta-sheet, fluorine, peptide, unnatural amino acid, Science, Organic chemistry, QD241-441
Abstract: Pentapeptides having the sequence R-HN-Ala-Val-X-Val-Leu-OMe, where the central residue X is L-serine, L-threonine, (2S,3R)-L-CF3-threonine and (2S,3S)-L-CF3-threonine were prepared. The capacity of (2S,3S)- and (2S,3R)-CF3-threonine analogues to stabilize an extended structure when introduced in the central position of pentapeptides is demonstrated by NMR conformational studies and molecular dynamics simulations. CF3-threonine containing pentapeptides are more prone to mimic β-strands than their natural Ser and Thr pentapeptide analogues. The proof of concept that these fluorinated β-strand mimics are able to disrupt protein–protein interactions involving β-sheet structures is provided. The CF3-threonine containing pentapeptides interact with the amyloid peptide Aβ1-42 in order to reduce the protein–protein interactions mediating its aggregation process.
Published: 2017
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3. Insight into the mechanism of action of temporin-SHa, a new broad-spectrum antiparasitic and antibacterial agent.

Author: Zahid Raja, Sonia André, Feten Abbassi, Vincent Humblot, Olivier Lequin, Tahar Bouceba, Isabelle Correia, Sandra Casale, Thierry Foulon, Denis Sereno, Bruno Oury, and Ali Ladram
Subjects: Medicine, Science
Abstract: Antimicrobial peptides (AMPs) are promising drugs to kill resistant pathogens. In contrast to bacteria, protozoan parasites, such as Leishmania, were little studied. Therefore, the antiparasitic mechanism of AMPs is still unclear. In this study, we sought to get further insight into this mechanism by focusing our attention on temporin-SHa (SHa), a small broad-spectrum AMP previously shown to be active against Leishmania infantum. To improve activity, we designed analogs of SHa and compared the antibacterial and antiparasitic mechanisms. [K3]SHa emerged as a highly potent compound active against a wide range of bacteria, yeasts/fungi, and trypanosomatids (Leishmania and Trypanosoma), with leishmanicidal intramacrophagic activity and efficiency toward antibiotic-resistant strains of S. aureus and antimony-resistant L. infantum. Multipassage resistance selection demonstrated that temporins-SH, particularly [K3]SHa, are not prone to induce resistance in Escherichia coli. Analysis of the mode of action revealed that bacterial and parasite killing occur through a similar membranolytic mechanism involving rapid membrane permeabilization and depolarization. This was confirmed by high-resolution imaging (atomic force microscopy and field emission gun-scanning electron microscopy). Multiple combined techniques (nuclear magnetic resonance, surface plasmon resonance, differential scanning calorimetry) allowed us to detail peptide-membrane interactions. [K3]SHa was shown to interact selectively with anionic model membranes with a 4-fold higher affinity (KD = 3 x 10-8 M) than SHa. The amphipathic α-helical peptide inserts in-plane in the hydrophobic lipid bilayer and disrupts the acyl chain packing via a detergent-like effect. Interestingly, cellular events, such as mitochondrial membrane depolarization or DNA fragmentation, were observed in L. infantum promastigotes after exposure to SHa and [K3]SHa at concentrations above IC50. Our results indicate that these temporins exert leishmanicidal activity via a primary membranolytic mechanism but can also trigger apoptotis-like death. The many assets demonstrated for [K3]SHa make this small analog an attractive template to develop new antibacterial/antiparasitic drugs.
Published: 2017
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4. Two consecutive aza-amino acids in peptides promote stable β-turn formation in water

Author: Chenghui Shi, Isabelle Correia, Nicolo Tonali, Sandrine Ongeri, and Olivier Lequin
Subjects: Organic Chemistry, Molecular Conformation, Water, Peptidomimetics, Amino Acids, Physical and Theoretical Chemistry, Peptides, Biochemistry
Abstract: Studies on the synthetic methodologies and the structural propensity of peptides containing consecutive aza-amino acids are still in their infancy. Here, details of the synthesis and conformational analysis of tripeptides containing two consecutive aza-amino acids are provided. The demonstration that the type I β-turn folding is induced, even in aqueous media, by the introduction of one or two lateral chains on the diaza-peptide unit is of particular importance for the design of peptidomimetics of biological interest.
Published: 2022
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5. 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
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6. 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
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7. Reprogramming Escherichia coli for the production of prenylated indole diketopiperazine alkaloids

Author: Nicolas Canu, Muriel Gondry, Isabelle Correia, Pascal Belin, Robert Thai, Olivier Lequin, Isabelle Jacques, Pavlina Dubois, Steven G. DuBois, Fabien Le Chevalier, Mireille Moutiez, 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), 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 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), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), This work was supported by the French Alternative Energies and Atomic Energy Commission (CEA), the French National Centre for Scientific Research (CNRS), the Sorbonne University and the French National Research Agency (grant ANR-16-CE29-0026)., We thank Dr Taek Soon Lee and Melanya Gudzeva from the Lawrence Berkeley National Laboratory for providing us with plasmids pJBEI-3085 and pJBEI-3122., ANR-16-CE29-0026,DKP-COMBIBIO,L'utilisation des voies de biosynthèse dépendant des synthases de cyclodipeptides pour obtenir de nouvelles 2,5-dicétopipérazines bioactives(2016), 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 Pierre et Marie Curie - Paris 6 (UPMC), Institute of Neurosciences and Psychology [Glasgow], University of Glasgow, Institut de Neurosciences de la Timone (INT), and Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Stereochemistry, [SDV]Life Sciences [q-bio], lcsh:Medicine, Context (language use), Diketopiperazines, medicine.disease_cause, Article, Indole Alkaloids, 03 medical and health sciences, 0302 clinical medicine, medicine, Escherichia coli, Moiety, [CHIM]Chemical Sciences, Author Correction, lcsh:Science, 2. Zero hunger, chemistry.chemical_classification, Indole test, Prenylation, Multidisciplinary, Chemistry, Alkaloid, lcsh:R, Bioproduction, 030104 developmental biology, Enzyme, Biocatalysis, lcsh:Q, Mevalonate pathway, Genetic Engineering, Metabolic engineering, 030217 neurology & neurosurgery
Abstract: Prenylated indole diketopiperazine (DKP) alkaloids are important bioactive molecules or their precursors. In the context of synthetic biology, efficient means for their biological production would increase their chemical diversification and the discovery of novel bioactive compounds. Here, we prove the suitability of the Escherichia coli chassis for the production of prenylated indole DKP alkaloids. We used enzyme combinations not found in nature by co-expressing bacterial cyclodipeptide synthases (CDPSs) that assemble the DKP ring and fungal prenyltransferases (PTs) that transfer the allylic moiety from the dimethylallyl diphosphate (DMAPP) to the indole ring of tryptophanyl-containing cyclodipeptides. Of the 11 tested combinations, seven resulted in the production of eight different prenylated indole DKP alkaloids as determined by LC-MS/MS and NMR characterization. Two were previously undescribed. Engineering E. coli by introducing a hybrid mevalonate pathway for increasing intracellular DMAPP levels improved prenylated indole DKP alkaloid production. Purified product yields of 2–26 mg/L per culture were obtained from culture supernatants. Our study paves the way for the bioproduction of novel prenylated indole DKP alkaloids in a tractable chassis that can exploit the cyclodipeptide diversity achievable with CDPSs and the numerous described PT activities.
Published: 2019
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8. Synthesis and Characterization of Hairpin Mimics that Modulate the Early Oligomerization and Fibrillization of Amyloid β-Peptide

Author: Dimitri Brinet, Umberto Piarulli, Guillaume Bernadat, Roberto Fanelli, Julia Kaffy, Sandrine Ongeri, Myriam Taverna, Leila Vahdati, Isabelle Correia, Silvia Panzeri, and Olivier Lequin
Subjects: 0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, Chemistry, Organic Chemistry, Biophysics, Physical and Theoretical Chemistry, Amyloid β peptide
Published: 2017
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9. Introducing sequential aza--amino acids units induces repeated β--turns and helical conformations in peptides

Author: Olivier Lequin, Jacopo Lesma, Guillaume Bernadat, Nicolo Tonali, Isabelle Correia, Sandrine Ongeri, Gestionnaire, HAL Sorbonne Université 5, Biomolécules : Conception, Isolement, Synthèse (BioCIS), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-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), 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), and 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)
Subjects: Stereochemistry, Protein Conformation, In silico, Proteolysis, 010402 general chemistry, 01 natural sciences, Biochemistry, 310 helix, Small peptide, [CHIM] Chemical Sciences, Side chain, medicine, [CHIM]Chemical Sciences, heterocyclic compounds, Physical and Theoretical Chemistry, Amino Acids, neoplasms, chemistry.chemical_classification, Aza Compounds, medicine.diagnostic_test, 010405 organic chemistry, Organic Chemistry, 0104 chemical sciences, Amino acid, stomatognathic diseases, chemistry, Selectivity, Peptides
Abstract: International audience; A major current issue in medicinal chemistry is the design of small peptide analogues resistant to proteolysis and able to adopt preferential conformations, while preserving the selectivity and efficiency of natural peptides. Whereas the introduction of one aza-Gly in peptides has proven numerous biological and structural interest, the conformational effect of sequential aza-Gly or aza-amino acids bearing side chains has not been investigated. In this work, experimental NMR and X-ray data together with in silico conformational studies reveal that the introduction of two consecutive aza-amino acids in pseudotripeptides induces the formation of stable hydrogen-bonded β-turn structures. Notably, this stabilization effect relies on the presence of side chains on aza-amino acids, as more flexible conformations are observed with aza-Gly residues. Remarkably, a longer aza/aza/α/aza/aza/α pseudohexapeptide containing substituted aza-amino acids adopts repeated β-turns conformations which interconvert with a fully helical structure mimicking a 3 10 helix.
Published: 2020
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10. Novel Matrix Metalloproteinase 12 Selective Radiotracers for Vascular Molecular Imaging

Author: Hye-Yeong Kim, Yunpeng Ye, Olivier Lequin, Jae-Joon Jung, Kiran Babu Gona, Vincent Dive, Fabrice Beau, Mahmoud Razavian, Isabelle Correia, Jakub Toczek, Mehran M. Sadeghi, Dimitris Georgiadis, Laurent Devel, Thomas Bordenave, Université Joseph Fourier - Grenoble 1 (UJF), Centre de recherche du CEA/DSV/iBiTec-S/SIMOPRO, Université Pierre et Marie Curie - Paris 6 (UPMC), 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), Yale School of Medicine [New Haven, Connecticut] (YSM), University of Athens, Athens, 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: Male, Biodistribution, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Matrix metalloproteinase, Matrix Metalloproteinase Inhibitors, 01 natural sciences, Article, 03 medical and health sciences, Aortic aneurysm, Mice, In vivo, medicine.artery, Matrix Metalloproteinase 12, Drug Discovery, medicine, Animals, Humans, [CHIM]Chemical Sciences, Tissue Distribution, Radioactive Tracers, Aorta, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Metalloproteinase, Radiochemistry, Chemistry, Organotechnetium Compounds, medicine.disease, Molecular biology, In vitro, 0104 chemical sciences, Molecular Imaging, Up-Regulation, Mice, Inbred C57BL, 010404 medicinal & biomolecular chemistry, cardiovascular system, Molecular Medicine, Molecular imaging, Aortic Aneurysm, Abdominal
Abstract: Matrix metalloproteinase-12 (MMP-12) is highly upregulated in several inflammatory diseases, including abdominal aortic aneurysm (AAA). Here we report four novel (99m)Tc-labeled radiotracers derived from a highly selective competitive MMP-12 inhibitor. These tracers in their (99g)Tc version were assessed in vitro on a set of human metalloproteases and displayed high affinity and selectivity toward MMP-12. Their radiolabeling with (99m)Tc was shown to be efficient and stable in both buffer and mouse blood. The tracers showed major differences in their biodistribution and blood clearance. Based on its in vivo performance, [(99m)Tc]-1 was selected for evaluation in murine AAA, where MMP-12 gene expression is upregulated. Autoradiography of aortae at two hours post-injection revealed high uptake of [(99m)Tc]-1 in AAA relative to adjacent aorta. Tracer uptake specificity was demonstrated through in vivo competition. This study paves the way for further evaluation of [(99m)Tc]-1 for imaging AAA and other MMP-12-associated diseases.
Published: 2019
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11. Author Correction: Reprogramming Escherichia coli for the production of prenylated indole diketopiperazine alkaloids

Author: Pavlina Dubois, Robert Thai, Mireille Moutiez, Steven G. DuBois, Muriel Gondry, Pascal Belin, Isabelle Correia, Nicolas Canu, Fabien Le Chevalier, Olivier Lequin, Isabelle Jacques, Enzymologie et Biosynthèse Peptidique Non Ribosomale (BIOSYN), Département Microbiologie (Dpt Microbio), 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 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), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
Subjects: Indole test, 0303 health sciences, Multidisciplinary, Chemistry, [SDV]Life Sciences [q-bio], lcsh:R, lcsh:Medicine, medicine.disease_cause, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Biochemistry, Prenylation, medicine, lcsh:Q, lcsh:Science, Reprogramming, Escherichia coli, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Published: 2019
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12. Study of bicyclomycin biosynthesis in Streptomyces cinnamoneus by genetic and biochemical approaches

Author: Jérôme Seguin, Emmanuel Favry, Isabelle Correia, Jean-Luc Pernodet, Sylvie Lautru, Jerzy Witwinowski, Laëtitia Caraty, Mireille Moutiez, Matthieu Coupet, Corinne Saulnier, Olivier Lequin, Muriel Gondry, Pascal Belin, Emmanuelle Darbon, Antonio C. Ruzzini, 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), Microbiologie Moléculaire des Actinomycètes (ACTINO), Département Microbiologie (Dpt Microbio), 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), Enzymologie et Biosynthèse Peptidique Non Ribosomale (BIOSYN), Université Pierre et Marie Curie - Paris 6 (UPMC), 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 ANR-16-CE29-0026,DKP-COMBIBIO,L'utilisation des voies de biosynthèse dépendant des synthases de cyclodipeptides pour obtenir de nouvelles 2,5-dicétopipérazines bioactives(2016)
Subjects: 0301 basic medicine, Molecular biology, Termination factor, [SDV]Life Sciences [q-bio], 030106 microbiology, lcsh:Medicine, Diketopiperazines, Hydroxylation, Microbiology, Article, Bicyclomycin, 03 medical and health sciences, chemistry.chemical_compound, Biosynthesis, Bacterial transcription, Gene cluster, [CHIM]Chemical Sciences, Streptomyces cinnamoneus, lcsh:Science, Analytical biochemistry, Gene, ComputingMilieux_MISCELLANEOUS, Multidisciplinary, Molecular Structure, Chemistry, lcsh:R, Bridged Bicyclo Compounds, Heterocyclic, Streptomyces, Anti-Bacterial Agents, Biosynthetic Pathways, 3. Good health, 030104 developmental biology, Models, Chemical, Biochemistry, Genes, Bacterial, Multigene Family, Mutation, lcsh:Q, Isoleucine
Abstract: The 2,5-Diketopiperazines (DKPs) constitute a large family of natural products with important biological activities. Bicyclomycin is a clinically-relevant DKP antibiotic that is the first and only member in a class known to target the bacterial transcription termination factor Rho. It derives from cyclo-(l-isoleucyl-l-leucyl) and has an unusual and highly oxidized bicyclic structure that is formed by an ether bridge between the hydroxylated terminal carbon atom of the isoleucine lateral chain and the alpha carbon of the leucine in the diketopiperazine ring. Here, we paired in vivo and in vitro studies to complete the characterization of the bicyclomycin biosynthetic gene cluster. The construction of in-frame deletion mutants in the biosynthetic gene cluster allowed for the accumulation and identification of biosynthetic intermediates. The identity of the intermediates, which were reproduced in vitro using purified enzymes, allowed us to characterize the pathway and corroborate previous reports. Finally, we show that the putative antibiotic transporter was dispensable for the producing strain.
Published: 2019
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13. Incorporation of Non-canonical Amino Acids into 2,5-Diketopiperazines by Cyclodipeptide Synthases

Author: Olivier Lequin, Robert Thai, Mireille Moutiez, Jérôme Seguin, Nicolas Canu, Isabelle Correia, Muriel Gondry, Pascal Belin, 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), Enzymologie et Biosynthèse Peptidique Non Ribosomale (BIOSYN), Département Microbiologie (Dpt Microbio), 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 de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), 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), 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 et de Technologies de Saclay (IBITECS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Université Pierre et Marie Curie - Paris 6 (UPMC), 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, 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)-Université Pierre et Marie Curie - Paris 6 (UPMC), Synthèse, Structure et Fonction de Molécules Bioactives (SSFMB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), ANR-16-CE29-0026,DKP-COMBIBIO,L'utilisation des voies de biosynthèse dépendant des synthases de cyclodipeptides pour obtenir de nouvelles 2,5-dicétopipérazines bioactives(2016), and ANR-14-CE09-0021,CDPS-hijacker,Etude fonctionnelle et structurale pour comprendre comment les CDPS détournent des ARNt aminoacylés(2014)
Subjects: 0301 basic medicine, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV]Life Sciences [q-bio], Bioactive molecules, Molecular Conformation, Diketopiperazines, 010402 general chemistry, 01 natural sciences, Catalysis, chemistry.chemical_compound, 03 medical and health sciences, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [CHIM]Chemical Sciences, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Amino Acids, Peptide Synthases, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, Natural product, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Chemistry, General Chemistry, General Medicine, Amino acid, 0104 chemical sciences, Enzyme, 030104 developmental biology, Biochemistry, Non canonical, Biocatalysis, Chemical diversity, human activities
Abstract: International audience; The manipulation of natural product biosynthetic pathways is a powerful means of expanding the chemical diversity of bioactive molecules. 2,5-diketopiperazines (2,5-DKPs) have been widely developed by medicinal chemists, but their biological production is yet to be exploited. We introduce an in vivo method for incorporating non-canonical amino acids (ncAAs) into 2,5-DKPs using cyclodipeptide synthases (CDPSs), the enzymes responsible for scaffold assembly in many 2,5-DKP biosynthetic pathways. CDPSs use aminoacyl-tRNAs as substrates. We exploited the natural ability of aminoacyl-tRNA synthetases to load ncAAs onto tRNAs. We found 26 ncAAs to be usable as substrates by CDPSs, leading to the enzymatic production of approximately 200 non-canonical cyclodipeptides. CDPSs constitute an efficient enzymatic tool for the synthesis of highly diverse 2,5-DKPs. Such diversity could be further expanded, for example, by using various cyclodipeptide-tailoring enzymes found in 2,5-DKP biosynthetic pathways
Published: 2018
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14. The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

Author: Tap Ha-Duong, Benoit Crousse, Jean-Louis Soulier, Julia Kaffy, Yaochun Xu, Sandrine Ongeri, Isabelle Correia, Nadjib Kihal, Olivier Lequin, Équipe 'Molécules Fluorées et Chimie Médicinale' BioCIS, Centre National de la Recherche Scientifique (CNRS), Service de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, INSERM U944 Laboratoire de Pathologie et Virologie Moléculaire, Laboratoire de Pathologie et Virologie Moléculaire, Biomolécules : Conception, Isolement, Synthèse (BioCIS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine, Structure et Dynamique des Biomolécules (LBM-E3), Laboratoire des biomolécules (LBM UMR 7203), 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, 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)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Synthèse et structure de molécules d'interet pharmacologique (SSMIP), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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 National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), HAL UPMC, Gestionnaire, and Université Paris-Seine-Université Paris-Seine-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Stereochemistry, Beta sheet, Peptide, 010402 general chemistry, 01 natural sciences, Pentapeptide repeat, Full Research Paper, lcsh:QD241-441, Residue (chemistry), Molecular dynamics, lcsh:Organic chemistry, fluorine, [CHIM]Chemical Sciences, unnatural amino acid, lcsh:Science, chemistry.chemical_classification, 010405 organic chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, aggregation, beta-sheet, [CHIM.ORGA] Chemical Sciences/Organic chemistry, peptide, 0104 chemical sciences, Chemistry, chemistry, lcsh:Q
Abstract: Pentapeptides having the sequence R-HN-Ala-Val-X-Val-Leu-OMe, where the central residue X is L-serine, L-threonine, (2S,3R)-L-CF3-threonine and (2S,3S)-L-CF3-threonine were prepared. The capacity of (2S,3S)- and (2S,3R)-CF3-threonine analogues to stabilize an extended structure when introduced in the central position of pentapeptides is demonstrated by NMR conformational studies and molecular dynamics simulations. CF3-threonine containing pentapeptides are more prone to mimic β-strands than their natural Ser and Thr pentapeptide analogues. The proof of concept that these fluorinated β-strand mimics are able to disrupt protein–protein interactions involving β-sheet structures is provided. The CF3-threonine containing pentapeptides interact with the amyloid peptide Aβ1-42 in order to reduce the protein–protein interactions mediating its aggregation process.
Published: 2017
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15. Designed Glycopeptidomimetics Disrupt Protein–Protein Interactions Mediating Amyloid β-Peptide Aggregation and Restore Neuroblastoma Cell Viability

Author: Katia Fabiana Fera, Olivier Lequin, David Allsop, Jean-Louis Soulier, Benoit Crousse, Nicolo Tonali, Dimitri Brinet, Mark Taylor, Lucie Khemtémourian, Isabelle Correia, Anais R. F. Hoffmann, Sandrine Ongeri, Yasmine Iacone, Julia Kaffy, Myriam Taverna, INSERM U944 Laboratoire de Pathologie et Virologie Moléculaire, Laboratoire de Pathologie et Virologie Moléculaire, Université Pierre et Marie Curie - Paris 6 (UPMC), Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), École supérieure du professorat et de l'éducation - Académie de Grenoble (ESPE Grenoble), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Grenoble Alpes (UGA), Synthèse et structure de molécules d'interet pharmacologique (SSMIP), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Université Grenoble Alpes - École supérieure du professorat et de l'éducation - Académie de Grenoble (UGA ESPE Grenoble), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Équipe 'Molécules Fluorées et Chimie Médicinale' BioCIS, Centre National de la Recherche Scientifique (CNRS), Service de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, BioCIS, Université Paris-Sud - Paris 11 (UP11), PJGN\IRCGN, Structure et Dynamique des Biomolécules (LBM-E3), Laboratoire des biomolécules (LBM UMR 7203), 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)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-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)-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), Biomolécules : Conception, Isolement, Synthèse (BioCIS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine, Physico-chimie, pharmacotechnie, biopharmacie (PCPB), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 ( UPMC ), École normale supérieure - Paris ( ENS Paris ), École supérieure du professorat et de l'éducation - Académie de Grenoble ( ESPE Grenoble ), Université Savoie Mont Blanc ( USMB [Université de Savoie] [Université de Chambéry] ) -Université Grenoble Alpes ( UGA ), Synthèse et structure de molécules d'interet pharmacologique ( SSMIP ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Centre National de la Recherche Scientifique (CNRS), 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 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)-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), and Université Paris-Seine-Université Paris-Seine-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Amyloid, Peptidomimetic, Cell Survival, Peptide, Plasma protein binding, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Protein aggregation, Protein Aggregation, Pathological, Protein–protein interaction, 03 medical and health sciences, Neuroblastoma, Protein Aggregates, Structure-Activity Relationship, [ CHIM.ORGA ] Chemical Sciences/Organic chemistry, Cell Line, Tumor, Drug Discovery, Structure–activity relationship, Humans, Surface plasmon resonance, Nuclear Magnetic Resonance, Biomolecular, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, Amyloid beta-Peptides, Dose-Response Relationship, Drug, Molecular Structure, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Glycopeptides, Surface Plasmon Resonance, Peptide Fragments, 030104 developmental biology, Biochemistry, chemistry, Drug Design, Molecular Medicine, Peptidomimetics, Protein Binding
Abstract: International audience; How anti-Alzheimer’s drug candidates that reduce amyloid 1–42 peptide fibrillization interact with the most neurotoxic species is far from being understood. We report herein the capacity of sugar-based peptidomimetics to inhibit both Aβ1–42 early oligomerization and fibrillization. A wide range of bio- and physicochemical techniques, such as a new capillary electrophoresis method, nuclear magnetic resonance, and surface plasmon resonance, were used to identify how these new molecules can delay the aggregation of Aβ1–42. We demonstrate that these molecules interact with soluble oligomers in order to maintain the presence of nontoxic monomers and to prevent fibrillization. These compounds totally suppress the toxicity of Aβ1–42 toward SH-SY5Y neuroblastoma cells, even at substoichiometric concentrations. Furthermore, demonstration that the best molecule combines hydrophobic moieties, hydrogen bond donors and acceptors, ammonium groups, and a hydrophilic β-sheet breaker element provides valuable insight for the future structure-based design of inhibitors of Aβ1–42 aggregation.
Published: 2016
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16. Homochiral Ion-Pairing Assisted by π−π Stacking between Δ-[Ru(bpy)2(Hcmbpy)]2+and Δ-Trisphat: A Quantitative Investigation

Author: C. Cordier, and Hani Amouri, Isabelle Correia, Service de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Architectures Moléculaires (A.R.C), Institut Parisien de Chimie Moléculaire (IPCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 010405 organic chemistry, Chemistry, Organic Chemistry, Inorganic chemistry, Stacking, Cationic polymerization, Aromaticity, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, Ion, Dication, Inorganic Chemistry, Crystallography, chemistry.chemical_compound, TRISPHAT, [CHIM]Chemical Sciences, Physical and Theoretical Chemistry, ComputingMilieux_MISCELLANEOUS, Equilibrium constant, Stoichiometry
Abstract: The ion-pairing between the chiral Δ- or Λ-[Ru(bpy)2(Hcmbpy)]2+ (Δ1 or Λ1) and the Δ-Trisphat- (Δ2) (Hcmbpy = 4-carboxy-4‘-methyl-2,2-bipyridine and Trisphat = tris(tetrachlorobenzenediolato)phosphate(V)) is investigated in solution by means of 1H NMR spectroscopy. The Ru−Trisphat ion-pairing adopts two stoichiometries that exchange via a fast dynamic process. The equilibrium constants K and K‘ are calculated for the 1/1 and 1/2 Ru/Trisphat stoichiometries. The constant values are in agreement with Coulombic attractions assisted by a π−π stacking between the bpy ligands of the Ru cation and the aromatic rings of the Trisphat anion. The homochiral pairing is favored as opposed to the heterochiral one, as shown by the respective K‘ values of 4.46 × 105 vs 2.05 × 105 M-2. In the homochiral ion pair, the cationic and anionic propellers adequately fit to optimize the π-stacking interactions and to lead to a dication sandwiched by two anions at the highest Trisphat/Ru ratios.
Published: 2007
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17. New chaetoglobosins from maize infested byPhomopsis leptostromiformisfungi. Production, identification, and semi‒synthesis

Author: Odile Convert, Jean-Claude Cherton, Bruno Dennetiere, Isabelle Correia, Ludovic Burlot, Synthèse, interactions et réactivité en chimie organique et bioorganique (SIRCOB), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie Organique UA CNRS 453, Service de Biochimie, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre
Subjects: Phomopsis leptostromiformis, Chaetoglobosins, biology, Strain (chemistry), 010405 organic chemistry, Stereochemistry, Metabolite, Fungus, biology.organism_classification, 01 natural sciences, 0104 chemical sciences, Compound s, 010404 medicinal & biomolecular chemistry, chemistry.chemical_compound, Fungal metabolite, chemistry, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Two-dimensional nuclear magnetic resonance spectroscopy, ComputingMilieux_MISCELLANEOUS, Spectroscopy
Abstract: This paper deals with the cytotoxic chaetoglobosins obtained from culture on maize of the strains ATCC 26115 and MRC 2654 of the fungusPhomopsis leptostromiformisBoth strains produced, in more or less important amounts, the known chaetoglobosins M (1) and N (2). In addition, the new chaetoglobosin O (3), was isolated from the ATCC 26115 strain and characterized by HRMS and 2D NMR experiments. With the MRC 2654 strain, a fungal metabolite4, more polar than the chaetoglobosins M and N, was extracted and purified. Spectroscopic and chromatographic data of metabolite4led to its identification to the bridged chaetoglobosin named compoundS, which previously has been obtained by intramolecular Michael reaction on the chaetoglobosin M. Moreover, a methylation under Williamson conditions of the chaetoglobosin4resulted in the formation of the trimethylated chaetoglobosin5.
Published: 2003
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18. Synthesis and conformational studies of a stable peptidomimetic β-hairpin based on a bifunctional diketopiperazine turn inducer

Author: Roberto Fanelli, Olivier Lequin, Isabelle Correia, Leila Vahdati, Sandrine Ongeri, Umberto Piarulli, Guillaume Bernadat, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] ( IBMM ), Ecole Nationale Supérieure de Chimie de Montpellier ( ENSCM ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Molécules bioactives, conception, isolement et synthèse ( MBCIS ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Département de Chimie - ENS Paris, École normale supérieure - Paris ( ENS Paris ), Synthèse et structure de molécules d'interet pharmacologique ( SSMIP ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Fondazione CARIPLO [RE-D DRUG TRAIN 2010-1373], Ministero dell'Universita e della Ricerca [2010NRREPL], Dipartimento di Scienza e Alta Tecnologia [Como], Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), Molécules bioactives, conception, isolement et synthèse (MBCIS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Laboratoire des biomolécules (LBM UMR 7203), Université Pierre et Marie Curie - Paris 6 (UPMC)-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 National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Università dell’Insubria, Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), 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, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: Materials Chemistry2506 Metals and Alloys, Tetrapeptide, Peptidomimetic, Stereochemistry, Chemical shift, Chemistry (all), Sequence (biology), General Chemistry, Combinatorial chemistry, Catalysis, Turn (biochemistry), chemistry.chemical_compound, Molecular dynamics, chemistry, Materials Chemistry, Inducer, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Bifunctional, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology
Abstract: International audience; The design, synthesis and conformational studies of a new beta-hairpin mimic, 2, are described in this paper. The design towards hairpin 2 is based on the assembly of the bifunctional DKP-1 as a beta-turn inducer, a peptidomimetic strand, namely 5-amino-2-methoxybenzhydrazide, to stabilize the formation of beta-sheets, and finally a tetrapeptide sequence, GVVI, containing the hydrophobic residues Val, Ile and Gly. The synthesis of hairpin 2 was performed in solution while the formation of the beta-hairpin in protic solvents was proven by NMR investigations (H-1 and C-13 chemical shifts, vicinal coupling constants and ROEs) and corroborated by computational studies (Monte-Carlo conformational search, molecular dynamics and DFT calculations).
Published: 2015
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19. Leukoencephalopathy with cysts and hyperglycinemia may result from NFU1 deficiency

Author: Florence Habarou, Hélène Delpech, Isabelle Correia, Nathalie Boddaert, Mathilde Nizon, Anaïs Brassier, Claude Sardet, Chris Ottolenghi, Agnès Delahodde, Pascale de Lonlay, A. Slama, A. Boutron, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de radiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Hôpital Bicêtre, Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Centre Référence des Maladies Héréditaires du Métabolisme de l'Enfant et de l'Adulte [CHU Necker] (MaMEA Necker), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Institut de génétique et microbiologie [Orsay] (IGM), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Mitochondrial Diseases, Propionic Acidemia, Hyperglycinemia, Fibroblasts/enzymology, Urine, medicine.disease_cause, Leukoencephalopathy, chemistry.chemical_compound, Plasma, Leukoencephalopathies, Child, Pyruvate Dehydrogenase Complex Deficiency Disease, Cerebrospinal Fluid, Cerebrospinal Fluid/chemistry, Mutation, medicine.diagnostic_test, Cysts, Mitochondrial Diseases/metabolism, 3. Good health, Pyruvate dehydrogenase deficiency, Cysts/*genetics, Europe, Lipoic acid, Pyruvate Dehydrogenase Complex Deficiency Disease/metabolism, Mitochondrial respiratory chain, Child, Preschool, Lactates, Molecular Medicine, Female, Leukoencephalopathies/*genetics, Proteins/chemistry, medicine.medical_specialty, Lactates/analysis, Carrier Proteins/*genetics, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Western blot, Internal medicine, medicine, Humans, Preschool, Molecular Biology, Protein Processing, Propionic Acidemia/*genetics, Post-Translational, Proteins, Cell Biology, Fibroblasts, medicine.disease, Plasma/chemistry, Endocrinology, chemistry, Urine/chemistry, Glycine, Carrier Proteins, Protein Processing, Post-Translational
Abstract: Lipoic acid metabolism defects are new metabolic disorders that cause neurological, cardiomuscular or pulmonary impairment. We report on a patient that presented with progressive neurological regression suggestive of an energetic disease, involving leukoencephalopathy with cysts. Elevated levels of glycine in plasma, urine and CSF associated with intermittent increases of lactate were consistent with a defect in lipoic acid metabolism. Support for the diagnosis was provided by pyruvate dehydrogenase deficiency and multiple mitochondrial respiratory chain deficiency in skin fibroblasts, as well as no lipoylated protein by western blot. Two mutations in the NFU1 gene confirmed the diagnosis. The p.Gly208Cys mutation has previously been reported suggesting a founder effect in Europe.
Published: 2014
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20. Mutations in human lipoyltransferase gene LIPT1cause a Leigh disease with secondary deficiency for pyruvate and alpha-ketoglutarate dehydrogenase

Author: Agnès Delahodde, Luc Nonnenmacher, Laurence Hubert, Yohan Soreze, A. Boutron, Florence Habarou, Hélène Delpech, Patrick Nitschke, Nathalie Boddaert, Chris Ottolenghi, Dominique Chretien, Christine Barnerias, Christine Bole-Feysot, Asmaa Mamoune, Claude Sardet, Pascale de Lonlay, Isabelle Correia, Yamina Hamel, Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Service de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Physiologie Cellulaire des Regulations Hormonales, Nutritionnelles et Pharmacologiques, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Unité de Neurologie, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Plateforme de génomique [Necker], Structure Fédérative de Recherche Necker ( SFR Necker - UMS 3633 / US24 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Plate Forme Paris Descartes de Bioinformatique ( BIP-D ), Université Paris Descartes - Paris 5 ( UPD5 ), Institut de génétique et microbiologie [Orsay] ( IGM ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), This work was supported by the Société Française des Erreurs Innées du Métabolisme Adulte (SFEIMA) to YS, Association Française contre les Myopathies [grant number 15947], Fondation Bettencourt to AM, Connaître les Syndromes Cérébelleux to AM, Association Noa Luu, Association Nos Anges and Fondation Lejeune [grant 2011 - 2012]., Plateforme de génomique [SFR Necker], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Pharmacologie, toxicologie et signalisation cellulaire (U747), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Plate Forme Paris Descartes de Bioinformatique (BIP-D), Université Paris Descartes - Paris 5 (UPD5), Institut de génétique et microbiologie [Orsay] (IGM), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and BMC, Ed.
Subjects: Pyruvate decarboxylation, Pyruvate dehydrogenase kinase, Immunoblotting, [SDV.GEN] Life Sciences [q-bio]/Genetics, Biology, Pyruvate dehydrogenase phosphatase, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Humans, LIPT1, Ketoglutarate Dehydrogenase Complex, Pyruvate Dehydrogenase (Lipoamide), Genetics(clinical), Pharmacology (medical), Alphaketoglutarate dehydrogenase lipoic acid, Amino Acids, Cells, Cultured, Genetics (clinical), 030304 developmental biology, Medicine(all), [SDV.GEN]Life Sciences [q-bio]/Genetics, 0303 health sciences, Thioctic Acid, Leigh disease, Research, Ketone Oxidoreductases, General Medicine, Fibroblasts, Pyruvate dehydrogenase complex, Molecular biology, Lipoic acid, chemistry, Biochemistry, lipids (amino acids, peptides, and proteins), Pyruvate dehydrogenase, Carrier Proteins, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Oxoglutarate dehydrogenase complex, Branched-chain alpha-keto acid dehydrogenase complex, Acyltransferases, 030217 neurology & neurosurgery
Abstract: International audience; BACKGROUND: Synthesis and apoenzyme attachment of lipoic acid have emerged as a new complex metabolic pathway. Mutations in several genes involved in the lipoic acid de novo pathway have recently been described, but no mutation was found so far in genes involved in the specific process of attachment of lipoic acid to apoenzymes pyruvate dehydrogenase (PDHc), alpha-ketoglutarate dehydrogenase (alpha-KGDHc) and branched chain alpha-keto acid dehydrogenase (BCKDHc) complexes. METHODS: Exome capture was performed in a boy who developed Leigh disease following a gastroenteritis and had combined PDH and alpha-KGDH deficiency with a unique amino acid profile that partly ressembled E3 subunit (dihydrolipoamide dehydrogenase / DLD) deficiency. Functional studies on patient fibroblasts were performed. Lipoic acid administration was tested on the LIPT1 ortholog lip3 deletion strain yeast and on patient fibroblasts. RESULTS: Exome sequencing identified two heterozygous mutations (c.875C > G and c.535A > G) in the LIPT1 gene that encodes a mitochondrial lipoyltransferase which is thought to catalyze the attachment of lipoic acid on PDHc, alpha-KGDHc, and BCKDHc. Anti-lipoic acid antibodies revealed absent expression of PDH E2, BCKDH E2 and alpha-KGDH E2 subunits. Accordingly, the production of 14CO2 by patient fibroblasts after incubation with 14Cglucose, 14Cbutyrate or 14C 3OHbutyrate was very low compared to controls. cDNA transfection experiments on patient fibroblasts rescued PDH and alpha-KGDH activities and normalized the levels of pyruvate and 3OHbutyrate in cell supernatants. The yeast lip3 deletion strain showed improved growth on ethanol medium after lipoic acid supplementation and incubation of the patient fibroblasts with lipoic acid decreased lactate level in cell supernatants. CONCLUSION: We report here a putative case of impaired free lipoic acid attachment due to LIPT1 mutations as a cause of PDH and alpha-KGDH deficiencies. Our study calls for renewed efforts to understand the mechanisms of pathology of lipoic acid-related defects and their heterogeneous biochemical expression, in order to devise efficient diagnostic procedures and possible therapies.
Published: 2013
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21. An active site mutant of Escherichia coli cyclopropane fatty acid synthase forms new non-natural fatty acids providing insights on the mechanism of the enzymatic reaction

Author: Dominique Guianvarc'h, Isabelle Correia, Olivier Ploux, Thierry Drujon, Guangqi E, Synthèse, Structure et Fonction de Molécules Bioactives (SSFMB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Laboratoire Charles Friedel, Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Analyse, Interactions Moléculaires et Cellulaires (LBM-E2), Laboratoire des biomolécules (LBM UMR 7203), 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, 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)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire de Chimie de la Matière Condensée de Paris (site Paris VI) (LCMCP (site Paris VI)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Pierre et Marie Curie - Paris 6 (UPMC)-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 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)-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)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cyclopropanation, Stereochemistry, Mutant, medicine.disease_cause, Biochemistry, Cyclopropane, Mycolic acid, 03 medical and health sciences, chemistry.chemical_compound, Catalytic Domain, medicine, Escherichia coli, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Nuclear Magnetic Resonance, Biomolecular, Fatty acid methyl ester, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, biology, 030306 microbiology, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Fatty Acids, Fatty acid, Active site, Esters, General Medicine, Methyltransferases, chemistry, Amino Acid Substitution, biology.protein
Abstract: International audience; : We have produced and purified an active site mutant of the Escherichia coli cyclopropane fatty acid synthase (CFAS) by replacing the strictly conserved G236 within cyclopropane synthases, by a glutamate residue, which corresponds to E146 of the homologous mycolic acid methyltransferase, Hma, producing hydroxymethyl mycolic acids. The G236E CFAS mutant had less than 1% of the in vitro activity of the wild type enzyme. We expressed the G236E CFAS mutant in an E. coli (DE3) strain in which the chromosomal cfa gene had been deleted. After extraction of phospholipids and conversion into the corresponding fatty acid methyl esters (FAMEs), we observed the formation of cyclopropanated FAMEs suggesting that the mutant retained some of the normal activity in vivo. However, we also observed the formation of new C17 methyl-branched unsaturated FAMEs whose structures were determined using GC/MS and NMR analyses. The double bond was located at different positions 8, 9 or 10, and the methyl group at position 10 or 9. Thus, this new FAMEs are likely arising from a 16:1 acyl chain of a phospholipid that had been transformed by the G236E CFAS mutant in vivo. The reaction catalyzed by this G236E CFAS mutant thus starts by the methylation of the unsaturated acyl chain at position 10 or 9 yielding a carbocation at position 9 or 10 respectively. It follows then two competing steps, a normal cyclopropanation or hydride shift/elimination events giving different combinations of alkenes. This study not only provides further evidence that cyclopropane synthases (CSs) form a carbocationic intermediate but also opens the way to CSs engineering for the synthesis of non-natural fatty acids.
Published: 2013
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22. Mitochondrial Infantile Liver Disease due to TRMU Gene Mutations: Three New Cases

Author: Philippe Labrune, Emmanuel Jacquemin, Pauline Gaignard, Oanez Ackermann, Isabelle Correia, Patrice Therond, Abdelhamid Slama, and Emmanuel Gonzales
Subjects: Genetics, Mitochondrial DNA, business.industry, Mitochondrial translation, Respiratory chain complex, Respiratory chain, Gene mutation, DGUOK, Bioinformatics, Article, Medicine, business, MPV17, Gene
Abstract: Combined respiratory chain defect is a common feature in mitochondrial liver disease during early infancy. Mitochondrial DNA depletions, induced by mutations of the nuclear genes POLG, DGUOK, and MPV17, are the major causes of these combined deficiencies. More recently, mutations in TRMU gene encoding the mitochondrial tRNA-specific 2-thiouridylase were found in infantile hepatopathy related to mitochondrial translation defect. It is characterized by a combined defect of respiratory chain complexes without mitochondrial DNA depletion.We report here clinical, biochemical, and genetic findings from three unrelated children presenting with hepatopathy associated with hyperlactatemia and respiratory chain defect due to bi-allelic mutations in TRMU gene. Two patients recovered spontaneously in a few months, whereas the other one died of acute liver failure. Spontaneous remission is a rare feature in mitochondrial liver diseases, and early identification of TRMU mutations could impact on clinical management. Our results extend the small number of TRMU mutations reported in mitochondrial liver disorders and allowed accumulating data for genotype-phenotype correlation.
Published: 2013
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23. Membrane interactions of two arginine-rich peptides with different cell internalization capacities

Author: Astrid Walrant, Sandrine Sagan, Isabelle Correia, Isabel D. Alves, Alexander Vogel, Olivier Lequin, Bernard Desbat, Bjoern E.S. Olausson, Institute of Economics, Leuphana University Lüneburg, Université Pierre et Marie Curie - Paris 6 (UPMC), Synthèse, Structure et Fonction de Molécules Bioactives (SSFMB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-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), Institute for Botany and Molecular Genetics, Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Service de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Structure et Dynamique des Biomolécules (LBM-E3), Laboratoire des biomolécules (LBM UMR 7203), 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, 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)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Université Sciences et Technologies - Bordeaux 1, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Université Pierre et Marie Curie - Paris 6 (UPMC)-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 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)-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), and Université Sciences et Technologies - Bordeaux 1 (UB)
Subjects: Models, Molecular, Attenuated Total Reflectance Infrared Spectroscopy, Magnetic Resonance Spectroscopy, Lipid Bilayers, Peptide, Cell-Penetrating Peptides, 01 natural sciences, Biochemistry, Spectroscopy, Fourier Transform Infrared, Membrane fluidity, Internalization, Lipid bilayer, Micelles, ComputingMilieux_MISCELLANEOUS, media_common, chemistry.chemical_classification, [PHYS]Physics [physics], 0303 health sciences, Peptide/lipid interaction, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Phosphatidylglycerols, Endocytosis, Protein Transport, Membrane, Phosphatidylcholines, Dimyristoylphosphatidylcholine, Protein Binding, media_common.quotation_subject, Biophysics, Molecular dynamics, Calorimetry, Molecular Dynamics Simulation, 010402 general chemistry, Arginine, 03 medical and health sciences, Membrane Lipids, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, Unilamellar Liposomes, 030304 developmental biology, Cell penetrating peptide, Cell Membrane, Biological membrane, Cell Biology, NMR, 0104 chemical sciences, Refractometry, Cell-penetrating peptide
Abstract: International audience; Cell penetrating peptides (CPPs) can cross cell membranes in a receptor independent manner and transport cargo molecules inside cells. These peptides can internalize through two independent routes: energy dependent endocytosis and energy independent translocation across the membrane, but the exact mechanisms are still unknown. The interaction of the CPP with different membrane components is certainly a preliminary key point that triggers internalization, such as the interaction with lipids to lead to the translocation process. In this study, we used two arginine-rich peptides, RW9 (RRWWRRWRR-NH(2)), which is a potent CPP, and RL9 (RRLLRRLRR-NH(2)) that, although binding tightly and accumulating on membranes, does not enter into cells. Using a set of experimental and theoretical techniques, we studied the binding, insertion and orientation of the peptides into different model membranes as well as the subsequent membrane reorganization. Herein we show that although the two peptides had rather similar behavior regarding lipid membrane interaction, subtle differences were found concerning the depth of peptide insertion, effect on the lipid chain ordering and kinetics of peptide insertion in the membrane, which altogether might explain their different cell internalization capacities. Molecular dynamics simulation studies show that some peptide molecules flipped their orientation over the course of the simulation such that the hydrophobic residues penetrated deeper in the lipid core region while Arg-residues maintained H-bonds with the lipid headgroups, serving as a molecular hinge in a conformation that appeared to correspond to the equilibrium one.
Published: 2012
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24. Sugar-based peptidomimetics inhibit amyloid β-peptide aggregation

Author: Bertrand Dorgeret, Olivier Lequin, Isabelle Correia, Jean-Louis Soulier, Lucie Khemtémourian, Sandrine Ongeri, Structure et Dynamique des Biomolécules (LBM-E3), Laboratoire des biomolécules (LBM UMR 7203), Université Pierre et Marie Curie - Paris 6 (UPMC)-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 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)-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), Service de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, INSERM U944 Laboratoire de Pathologie et Virologie Moléculaire, Laboratoire de Pathologie et Virologie Moléculaire, Synthèse et structure de molécules d'interet pharmacologique (SSMIP), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université Sciences et Technologies - Bordeaux 1-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC), Synthèse, Structure et Fonction de Molécules Bioactives (SSFMB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), 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, 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)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Chimie et Biologie des Membranes et des Nanoobjets ( CBMN ), Université Sciences et Technologies - Bordeaux 1-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux ( ENITAB ) -Centre National de la Recherche Scientifique ( CNRS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Synthèse, Structure et Fonction de Molécules Bioactives ( SSFMB ), Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Synthèse et structure de molécules d'interet pharmacologique ( SSMIP ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), 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), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre
Subjects: Amyloid, Peptidomimetic, Kinetics, Peptide, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 010402 general chemistry, 01 natural sciences, Glucosides, Alzheimer Disease, [ CHIM.ORGA ] Chemical Sciences/Organic chemistry, Drug Discovery, Molecule, Humans, Sugar, Nuclear Magnetic Resonance, Biomolecular, ComputingMilieux_MISCELLANEOUS, Pharmacology, chemistry.chemical_classification, [PHYS]Physics [physics], Amyloid beta-Peptides, 010405 organic chemistry, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, P3 peptide, General Medicine, Fluorescence, 0104 chemical sciences, Islet Amyloid Polypeptide, Biochemistry, Peptidomimetics
Abstract: International audience; Alzheimer's disease is characterized by the oligomerization and amyloid fibril formation of amyloid β-peptide (Aβ). We describe a novel class of small water-soluble Aβ binding peptidomimetics based on two hydrophobic Ala-Val and Val-Leu dipeptides linked to a D-glucopyranosyl scaffold through aminoalkyl and carboxyethyl links in C1 and C6 positions. These compounds combine the targeting of hydrophobic recognition interfaces with an original hydrophilic sugar β-breakage strategy. These molecules were shown, by fluorescence thioflavin-T assays, to dramatically slow down the kinetics of amyloid fibril formation even at a low peptidomimetics to Aβ ratio of 0.1:1. Electron microscopy images revealed that the peptidomimetics efficiently reduced the amount of typical amyloid fibrils. NMR saturation transfer difference experiments indicated that these molecules interact with Aβ aggregated species through their hydrophobic amino acid residues. This inhibition effect was found to be sequence-specific since these molecules did not alter the kinetics of aggregation of another amyloid peptide, IAPP, involved in type 2 diabetes mellitus.
Published: 2011
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25. Different membrane behaviour and cellular uptake of three basic arginine-rich peptides

Author: Gérard Chassaing, Eric H. Bent, Nicole Goasdoué, Isabel D. Alves, Isabelle Correia, Claire Lacombe, Olivier Lequin, Astrid Walrant, Sandrine Sagan, Chen-Yu Jiao, Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Structure et Dynamique des Biomolécules (LBM-E3), Laboratoire des biomolécules (LBM UMR 7203), Université Pierre et Marie Curie - Paris 6 (UPMC)-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 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)-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), Synthèse, Structure et Fonction de Molécules Bioactives (SSFMB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Protéines : biochimie structurale et fonctionnelle (PBSF), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), 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, 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)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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 Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: Staphylococcus aureus, Magnetic Resonance Spectroscopy, Antimicrobial peptides, Molecular Sequence Data, Biophysics, Peptide, CHO Cells, Microbial Sensitivity Tests, Calorimetry, 010402 general chemistry, Arginine, 01 natural sciences, Biochemistry, Cell membrane, Polyarginine, 03 medical and health sciences, Cricetulus, Cellular uptake, Cricetinae, medicine, Escherichia coli, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, chemistry.chemical_classification, [PHYS]Physics [physics], 0303 health sciences, Cell penetrating peptide, Calorimetry, Differential Scanning, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Chinese hamster ovary cell, Vesicle, Circular Dichroism, Cell Membrane, Isothermal titration calorimetry, Cell Biology, NMR, 0104 chemical sciences, Anti-Bacterial Agents, Membrane, medicine.anatomical_structure, Cell-penetrating peptide, Peptide lipid interactions, Peptides
Abstract: International audience; Cell penetrating peptides (CPPs) are peptides displaying the ability to cross cell membranes and transport cargo molecules inside cells. Several uptake mechanisms (endocytic or direct translocation through the membrane) are being considered, but the interaction between the CPP and the cell membrane is certainly a preliminary key point to the entry of the peptide into the cell. In this study, we used three basic peptides: RL9 (RRLLRRLRR-NH(2)), RW9 (RRWWRRWRR-NH(2)) and R9 (RRRRRRRRR-NH(2)). While RW9 and R9 were internalised into wild type Chinese Hamster Ovary cells (CHO) and glycosaminoglycan-deficient CHO cells, at 4°C and 37°C, RL9 was not internalised into CHO cells. To better understand the differences between RW9, R9 and RL9 in terms of uptake, we studied the interaction of these peptides with model lipid membranes. The effect of the three peptides on the thermotropic phase behaviour of a zwitterionic lipid (DMPC) and an anionic lipid (DMPG) was investigated with differential scanning calorimetry (DSC). The presence of negative charges on the lipid headgroups appeared to be essential to trigger the peptide/lipid interaction. RW9 and R9 disturbed the main phase transition of DMPG, whereas RL9 did not induce significant effects. Isothermal titration calorimetry (ITC) allowed us to study the binding of these peptides to large unilamellar vesicles (LUVs). RW9 and R9 proved to have about ten fold more affinity for DSPG LUVs than RL9. With circular dichroism (CD) and NMR spectroscopy, the secondary structure of RL9, RW9 and R9 in aqueous buffer or lipid/detergent conditions was investigated. Additionally, we tested the antimicrobial activity of these peptides against Escherichia coli and Staphylococcus aureus, as CPPs and antimicrobial peptides are known to share several common characteristics. Only RW9 was found to be mildly bacteriostatic against E. coli. These studies helped us to get a better understanding as to why R9 and RW9 are able to cross the cell membrane while RL9 remains bound to the surface without entering the cell.
Published: 2011
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26. Membrane interaction and perturbation mechanisms induced by two cationic cell penetrating peptides with distinct charge distribution

Author: Isabel D. Alves, Sandrine Sagan, Nicole Goasdoué, Solange Lavielle, Gérard Chassaing, Soline Aubry, Isabelle Correia, Cécile Galanth, Synthèse, Structure et Fonction de Molécules Bioactives (SSFMB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC), Proteines Biochimie Structurale et Fonctionnelle (FRE 2852), Peptidome de la Peau des Amphibiens (FRE 2852), Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Léon Brillouin (LLB - UMR 12), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Sorbonne Université (SU), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
Subjects: Erythrocytes, Cooperativity, Cell-Penetrating Peptides, 01 natural sciences, Biochemistry, chemistry.chemical_compound, Cricetinae, Lipid bilayer, [PHYS]Physics [physics], 0303 health sciences, Calorimetry, Differential Scanning, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Vesicle, Bilayer, Circular Dichroism, Temperature, Phosphatidylglycerols, Klebsiella pneumoniae, Membrane, Ethanolamines, Fatty Acids, Unsaturated, Thermodynamics, Dimyristoylphosphatidylcholine, Staphylococcus aureus, Biophysics, Phospholipid, CHO Cells, Microbial Sensitivity Tests, 010402 general chemistry, 03 medical and health sciences, Cricetulus, Animals, Humans, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Molecular Biology, Nuclear Magnetic Resonance, Biomolecular, 030304 developmental biology, Phosphatidylethanolamine, Dose-Response Relationship, Drug, Cell Membrane, Phosphorus Isotopes, 0104 chemical sciences, chemistry, Models, Chemical, Liposomes, Cell-penetrating peptide, Bacillus megaterium, Carrier Proteins, Peptides, Antimicrobial Cationic Peptides
Abstract: International audience; Independently from the cell penetrating peptide uptake mechanism (endocytic or not), the interaction of the peptide with the lipid bilayer remains a common issue that needs further investigation. The cell penetrating or antimicrobial properties of exogenous peptides require probably different preliminary interactions with the plasma membrane. Herein, we have employed (31)P NMR, differential scanning calorimetry and CD to study the membrane interaction and perturbation mechanisms of two basic peptides with similar length but distinct charge distribution, penetratin (non-amphipathic) and RL16, a secondary amphipathic peptide. The peptide effects on the thermotropic phase behavior of large multilamellar vesicles of dimyristoylphosphatidylcholine (DMPC), dimyristoylphosphatidylglycerol (DMPG) and dipalmitoleoyl phosphatidylethanolamine (DiPoPE) were investigated. We have found that, even though both peptides are cationic, their interaction with zwitterionic versus anionic lipids is markedly distinct. Penetratin greatly affects the temperature, enthalpy and cooperativity of DMPG main phase transition but does not affect those of DMPC while RL16 presents opposite effects. Additionally, it was found that penetratin induces a negative curvature whereas RL16 induces a positive one, since a decrease in the fluid lamellar to inverted hexagonal phase transition temperature of DiPoPE (T(H)) was observed for penetratin and an increase for RL16. Contrary to penetratin, (31)P NMR of samples containing DMPC MLVs and RL16 shows an isotropic signal indicative of the formation of small vesicles, concomitant with a great decrease in sample turbidity both below and at the phase transition temperature. Opposite effects were also observed on DMPG where both peptides provoke strong aggregation and precipitation. Both CPPs adopt helical structures when contacting with anionic lipids, and possess a dual behavior by either presenting their cationic or hydrophobic domains towards the phospholipid face, depending on the lipid nature (anionic vs zwitterionic, respectively). Surprisingly, the increase of electrostatic interactions at the water membrane interface prevents the insertion of RL16 hydrophobic region in the bilayer, but is essential for the interaction of penetratin. Modulation of amphipathic profiles and charge distribution of CPPs can alter the balance of hydrophobic and electrostatic membrane interaction leading to translocation or and membrane permeabilisation. Penetratin has a relative pure CPP behavior whereas RL16 presents mixed CPP/AMP properties. A better understanding of those processes is essential to unveil their cell translocation mechanism.
Published: 2010
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27. The interaction of cell-penetrating peptides with lipid model systems and subsequent lipid reorganization: thermodynamic and structural characterization

Author: Gérard Chassaing, Emmanuelle Sachon, Isabelle Correia, Isabel D. Alves, Sandrine Sagan, Gordon Tollin, Solange Lavielle, Chen Yu Jiao, Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Biologie intégrative (FRBI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Department of Biochemistry and Molecular Biophysics, University of Arizona, Institut de Biologie Intégrative (IFR-BI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI 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: Magnetic Resonance Spectroscopy, Supramolecular chemistry, Phospholipid, Peptide, 010402 general chemistry, 01 natural sciences, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Structural Biology, Drug Discovery, Amphiphile, [CHIM]Chemical Sciences, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Pharmacology, chemistry.chemical_classification, [PHYS]Physics [physics], 0303 health sciences, Calorimetry, Differential Scanning, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Bilayer, Organic Chemistry, Cell Membrane, General Medicine, Lipids, 0104 chemical sciences, Membrane, Drug delivery, Biophysics, Cell-penetrating peptide, Molecular Medicine, Thermodynamics, Peptides
Abstract: International audience; Cell-penetrating peptides (CPPs) are cationic peptides that are able to induce cellular uptake and delivery of large and hydrophilic molecules, that otherwise do not cross the plasma membrane of eukaryotic cells. Despite their potential use for gene transfer and drug delivery, the mode of action of CPPs is still mysterious. Nonetheless, the interaction with phospholipid bilayers constitutes the first step in the process. The interaction of two CPPs with distinct charge distribution, penetratin (nonamphipathic) and RL16 (a secondary amphipathic peptide with antimicrobial properties) with lipid membranes was investigated. For this purpose, we employed three independent techniques, comprising (31)P-nuclear magnetic resonance, differential scanning calorimetry (DSC), and plasmon waveguide resonance (PWR) spectroscopy. In view of the cationic nature of the peptides, their interaction and affinity for zwitterionic versus anionic lipids was investigated. Although a strong affinity was observed when negative charged lipids were present, the peptides' thermodynamic behavior on binding to zwitterionic versus anionic lipids and the induced supramolecular structure organization in those lipids was quite different. The study suggests that the amphipathic profile and charge distribution of CPPs strongly influences the perturbation mechanism of the peptide on the bilayer establishing the frontier between a pure CPP and a CPP with antimicrobial properties.
Published: 2008
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28. Synthesis and conformational studies of pseudopeptides containing an unsymmetrical triazine scaffold

Author: Bertrand Dorgeret, Isabelle Correia, Gérard Chassaing, Erika Bourguet, Sandrine Ongeri, Sames Sicsic, Innovation Thérapeutique : du Fondamental au Médicament, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-MEDICEN-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Recherche Agronomique (INRA), Synthèse, Structure et Fonction de Molécules Bioactives (SSFMB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Biomolécules : Conception, Isolement, Synthèse (BioCIS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine, Service de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Université Pierre et Marie Curie - Paris 6 (UPMC), Synthèse et structure de molécules d'interet pharmacologique (SSMIP), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Paris-Sud - Paris 11 (UP11)-MEDICEN-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris-Sud - Paris 11 (UP11)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Seine-Université Paris-Seine-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre
Subjects: Models, Molecular, Scaffold, Protein Conformation, Peptidomimetic, Stereochemistry, Molecular Conformation, Peptide, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 010402 general chemistry, 01 natural sciences, Biochemistry, Protein Structure, Secondary, chemistry.chemical_compound, Biomimetic Materials, Structural Biology, Drug Discovery, [CHIM]Chemical Sciences, Amino Acid Sequence, Molecular Biology, Alkyl, ComputingMilieux_MISCELLANEOUS, Triazine, Pharmacology, chemistry.chemical_classification, Molecular Structure, Triazines, 010405 organic chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, Hydrogen Bonding, General Medicine, Combinatorial chemistry, Protein Structure, Tertiary, 0104 chemical sciences, chemistry, Molecular Medicine, Indicators and Reagents, Oligopeptides
Abstract: International audience; The versatile chloromethyl TIPNO-based alkoxyamine was efficiently transformed into other valuable functionalised TIPNO-based alkoxyamines such as amino alkoxyamines which are interesting initiators for block copolymers and bisalkoxyamines in good yield and in two steps at the most. One bisalkoxyamine has allowed to prepare well-defined polystyrene-b-poly(n-butyl acrylate)-b-polystyrene symmetrical triblock copolymer. The last representative example of such alkoxyamines is a styrenic alkoxyamine which was copolymerized with styrene to afford branched polystyrene. Finally, for the first time branched poly(n-butyl acrylate) by nitroxide mediated radical polymerization was obtained and was a efficient macroinitiator of styrene, which indicates that the radical polymerization mediated by this styrenic alkoxyamine is living.
Published: 2008
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29. Study of a potential inhibitor of acetylcholinesterase using UV spectrophotometry, NMR spectroscopy and molecular modeling

Author: Nello Ronzani, Isabelle Correia, Nicole Platzer, Jean-Claude Beloeil, Bich-Thuy Doan, Service de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-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 d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut de Chimie des Substances Naturelles (ICSN), and Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Subjects: [PHYS]Physics [physics], Molecular model, 010405 organic chemistry, medicine.drug_class, Stereochemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, Nuclear magnetic resonance spectroscopy, 010402 general chemistry, 01 natural sciences, Acetylcholinesterase, 0104 chemical sciences, Hydrophobic effect, chemistry.chemical_compound, chemistry, Acetylcholinesterase inhibitor, Docking (molecular), Acridine, medicine, Pyridinium, Physical and Theoretical Chemistry, ComputingMilieux_MISCELLANEOUS
Abstract: 1-[6-(Acridine-9-carbonyloxy)hexyl]pyridinium chloride (1) was synthesized and studied as a potential inhibitor of acetylcholinesterase (AChE), which is frequently involved in Alzheimer's disease. UV spectrophotometry showed that 1 is a reversible and competitive inhibitor of AChE (Ki ≈ 2 × 10−7 M). NMR (TrNOESY) showed that 1, bonded to AChE, maintains an extended form that allows hydrophobic interactions to occur between the aliphatic chain and the deep and narrow gorge of AchE and favors interactions between the acridine group and the catalytic and anionic subsites situated at the bottom of the gorge, and also between the pyridinium ring and the peripheral site. A more detailed picture of the structure of the complex was obtained by combining NMR structural data and molecular modeling (docking, dynamics simulation and energy calculations). Copyright © 2006 John Wiley & Sons, Ltd.
Published: 2006
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30. Study of inclusion complexes of acridine with β- and (2,6-di- O -methyl)-β-cyclodextrin by use of solubility diagrams and NMR spectroscopy

Author: Isabelle Correia, Nicole Platzer, Nello Ronzani, Bich-Thuy Doan, Nabil Bezzenine, Jean-Claude Beloeil, Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), and Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: chemistry.chemical_classification, Molecular model, Cyclodextrin, Stereochemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, Substituent, 02 engineering and technology, Nuclear magnetic resonance spectroscopy, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, 0104 chemical sciences, chemistry.chemical_compound, chemistry, Docking (molecular), Computational chemistry, Acridine, Proton NMR, [CHIM]Chemical Sciences, Physical and Theoretical Chemistry, Solubility, 0210 nano-technology, ComputingMilieux_MISCELLANEOUS
Abstract: Previous molecular modeling studies, in our laboratory, have shown that some esters of type RCOO(CH2)nC5H5N+Cl− are potentially active against Alzheimer's disease. We have also demonstrated that acridine, which has strong anticholinesterase activity appears to be a suitable R substituent. The main obstacle to the possible pharmaceutical application of these compounds is their limited solubility in water, which is due to the poor aqueous solubility of acridine itself (0.26 mM). Inclusion complexation with cyclodextrins may overcome this problem. Solubility diagrams and NMR spectroscopy were used to study the inclusion of acridine (Acr) within β-cyclodextrin (βCD) and heptakis(2,6-di-O-methyl)cyclomaltoheptose (DMβCD). A 1:1 complex was formed for the Acr–βCD system and both 1:1 and 2:1 complexes for the Acr–DMβCD system (apparent Ka 215 ± 20 and 1150 ± 100 M−1, respectively). Data from 1H NMR studies corrected the assignment of the acridine H1, H8 and H4, H5 protons in D2O, which have been erroneously assigned in previous publications. 1H spin–lattice relaxation times T1 measured with selective, non-selective and null inversion characterize the dynamics of the inclusion complexes. Geometric features of the host–guest inclusion complexes were inferred from intermolecular dipolar interactions obtained by 2D adiabatic off-resonance ROESY experiments. A more detailed picture of the structure of the inclusion complexes was obtained by combining NMR structural data and molecular modeling (docking, dynamics under NMR constraints and energy calculations). Copyright © 2002 John Wiley & Sons, Ltd.
Published: 2002
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31. Multiple selective excitation as a tool for NMR studies of paramagnetic metalloproteins

Author: Isabelle Correia, Didier Riviere, Nicole Goasdoué, Odile Convert, Mario Piccioli, Synthèse, Structure et Fonction de Molécules Bioactives (SSFMB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire de Chimie Organique UA CNRS 453, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), and Università degli Studi di Firenze = University of Florence (UniFI)
Subjects: chemistry.chemical_classification, Paramagnetism, Nuclear magnetic resonance, Chemistry, Metalloprotein, [CHIM]Chemical Sciences, General Materials Science, General Chemistry, Selective excitation, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2000
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32. Mahafacyclin A, a cyclic heptapeptide from Jatropha mahafalensis exhibiting β-bulge conformation

Author: Catherine Auvin-Guette, Bernard Bodo, Alain Blond, Jean-Louis Pousset, Isabelle Correia, Carine Baraguey, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Laboratoire de chimie et biochimie des substances naturelles, Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC), Department of Pharmacognosy, Faculty of Medicine, Poitiers, France, Molécules de Communication et Adaptation des Micro-organismes (MCAM), Laboratoire de chimie des substances naturelles : structure, synthèse et bio-activités des substances naturelles, Synthèse, Structure et Fonction de Molécules Bioactives (SSFMB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], 010405 organic chemistry, Chemistry, Stereochemistry, Organic Chemistry, Jatropha, 010402 general chemistry, biology.organism_classification, 01 natural sciences, Biochemistry, 0104 chemical sciences, Bulge, Drug Discovery, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Two-dimensional nuclear magnetic resonance spectroscopy, Chemical decomposition, ComputingMilieux_MISCELLANEOUS
Abstract: The structure of mahafacyclin A ( 1 ), a cyclic heptapeptide isolated from Jatropha mahafalensis latex was elucidated by a combination of chemical degradation, LSIMS data and 2D NMR experiments. Mahafacyclin A solution conformation was shown to have β-bulge characteristics.
Published: 2000
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33. Homochiral Ion-Pairing Assisted by − Stacking between -Ru(bpy)2(Hcmbpy)2and -Trisphat: A Quantitative Investigation.

Author: Isabelle Correia, Hani Amouri, and Christine Cordier
Published: 2007
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33 results on '"Isabelle Correia"'

1. In vivo characterization of the activities of novel cyclodipeptide oxidases: new tools for increasing chemical diversity of bioproduced 2,5-diketopiperazines in Escherichia coli

2. The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

3. Insight into the mechanism of action of temporin-SHa, a new broad-spectrum antiparasitic and antibacterial agent.

4. Two consecutive aza-amino acids in peptides promote stable β-turn formation in water

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

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

7. Reprogramming Escherichia coli for the production of prenylated indole diketopiperazine alkaloids

8. Synthesis and Characterization of Hairpin Mimics that Modulate the Early Oligomerization and Fibrillization of Amyloid β-Peptide

9. Introducing sequential aza--amino acids units induces repeated β--turns and helical conformations in peptides

10. Novel Matrix Metalloproteinase 12 Selective Radiotracers for Vascular Molecular Imaging

11. Author Correction: Reprogramming Escherichia coli for the production of prenylated indole diketopiperazine alkaloids

12. Study of bicyclomycin biosynthesis in Streptomyces cinnamoneus by genetic and biochemical approaches

13. Incorporation of Non-canonical Amino Acids into 2,5-Diketopiperazines by Cyclodipeptide Synthases

14. The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

15. Designed Glycopeptidomimetics Disrupt Protein–Protein Interactions Mediating Amyloid β-Peptide Aggregation and Restore Neuroblastoma Cell Viability

16. Homochiral Ion-Pairing Assisted by π−π Stacking between Δ-[Ru(bpy)2(Hcmbpy)]2+and Δ-Trisphat: A Quantitative Investigation

17. New chaetoglobosins from maize infested byPhomopsis leptostromiformisfungi. Production, identification, and semi‒synthesis

18. Synthesis and conformational studies of a stable peptidomimetic β-hairpin based on a bifunctional diketopiperazine turn inducer

19. Leukoencephalopathy with cysts and hyperglycinemia may result from NFU1 deficiency

20. Mutations in human lipoyltransferase gene LIPT1cause a Leigh disease with secondary deficiency for pyruvate and alpha-ketoglutarate dehydrogenase

21. An active site mutant of Escherichia coli cyclopropane fatty acid synthase forms new non-natural fatty acids providing insights on the mechanism of the enzymatic reaction

22. Mitochondrial Infantile Liver Disease due to TRMU Gene Mutations: Three New Cases

23. Membrane interactions of two arginine-rich peptides with different cell internalization capacities

24. Sugar-based peptidomimetics inhibit amyloid β-peptide aggregation

25. Different membrane behaviour and cellular uptake of three basic arginine-rich peptides

26. Membrane interaction and perturbation mechanisms induced by two cationic cell penetrating peptides with distinct charge distribution

27. The interaction of cell-penetrating peptides with lipid model systems and subsequent lipid reorganization: thermodynamic and structural characterization

28. Synthesis and conformational studies of pseudopeptides containing an unsymmetrical triazine scaffold

29. Study of a potential inhibitor of acetylcholinesterase using UV spectrophotometry, NMR spectroscopy and molecular modeling

30. Study of inclusion complexes of acridine with β- and (2,6-di- O -methyl)-β-cyclodextrin by use of solubility diagrams and NMR spectroscopy

31. Multiple selective excitation as a tool for NMR studies of paramagnetic metalloproteins

32. Mahafacyclin A, a cyclic heptapeptide from Jatropha mahafalensis exhibiting β-bulge conformation

33. Homochiral Ion-Pairing Assisted by − Stacking between -Ru(bpy)2(Hcmbpy)2and -Trisphat: A Quantitative Investigation.

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33 results on '"Isabelle Correia"'

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