8 results on '"Billard É"'
Search Results
2. 32 Impact of colibactin-producing escherichia coli on immune microenvironment in preclinical colorectal cancer models
- Author
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Lopes, A., Casse, A.H., Veziant, J., Roche, G., Barnich, N., Miot-Noirault, E., Naimi, S., Billard, E., Dumas, B., and Bonnet, M.
- Published
- 2018
- Full Text
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3. HIV-1 assembly in macrophages
- Author
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Benaroch Philippe, Billard Elisabeth, Gaudin Raphaël, Schindler Michael, and Jouve Mabel
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract The molecular mechanisms involved in the assembly of newly synthesized Human Immunodeficiency Virus (HIV) particles are poorly understood. Most of the work on HIV-1 assembly has been performed in T cells in which viral particle budding and assembly take place at the plasma membrane. In contrast, few studies have been performed on macrophages, the other major target of HIV-1. Infected macrophages represent a viral reservoir and probably play a key role in HIV-1 physiopathology. Indeed macrophages retain infectious particles for long periods of time, keeping them protected from anti-viral immune response or drug treatments. Here, we present an overview of what is known about HIV-1 assembly in macrophages as compared to T lymphocytes or cell lines. Early electron microscopy studies suggested that viral assembly takes place at the limiting membrane of an intracellular compartment in macrophages and not at the plasma membrane as in T cells. This was first considered as a late endosomal compartment in which viral budding seems to be similar to the process of vesicle release into multi-vesicular bodies. This view was notably supported by a large body of evidence involving the ESCRT (Endosomal Sorting Complex Required for Transport) machinery in HIV-1 budding, the observation of viral budding profiles in such compartments by immuno-electron microscopy, and the presence of late endosomal markers associated with macrophage-derived virions. However, this model needs to be revisited as recent data indicate that the viral compartment has a neutral pH and can be connected to the plasma membrane via very thin micro-channels. To date, the exact nature and biogenesis of the HIV assembly compartment in macrophages remains elusive. Many cellular proteins potentially involved in the late phases of HIV-1 cycle have been identified; and, recently, the list has grown rapidly with the publication of four independent genome-wide screens. However, their respective roles in infected cells and especially in macrophages remain to be characterized. In summary, the complete process of HIV-1 assembly is still poorly understood and will undoubtedly benefit from the ongoing explosion of new imaging techniques allowing better time-lapse and quantitative studies.
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- 2010
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4. Lipidated peptides derived from intracellular loops 2 and 3 of the urotensin II receptor act as biased allosteric ligands.
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Nassour H, Hoang TA, Martin RD, Dallagnol JCC, Billard É, Létourneau M, Novellino E, Carotenuto A, Allen BG, Tanny JC, Fournier A, Hébert TE, and Chatenet D
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- Allosteric Regulation, Cell Proliferation, HEK293 Cells, Humans, Intracellular Signaling Peptides and Proteins chemistry, Intracellular Signaling Peptides and Proteins genetics, Ligands, Peptide Hormones chemistry, Peptide Hormones genetics, Peptides chemistry, Protein Conformation, alpha-Helical, Receptors, G-Protein-Coupled genetics, Signal Transduction, Intracellular Signaling Peptides and Proteins metabolism, Peptide Hormones metabolism, Peptides metabolism, Receptors, G-Protein-Coupled chemistry, Receptors, G-Protein-Coupled metabolism
- Abstract
Over the last decade, the urotensinergic system, composed of one G protein-coupled receptor and two endogenous ligands, has garnered significant attention as a promising new target for the treatment of various cardiovascular diseases. Indeed, this system is associated with various biomarkers of cardiovascular dysfunctions and is involved in changes in cardiac contractility, fibrosis, and hypertrophy contributing, like the angiotensinergic system, to the pathogenesis and progression of heart failure. Significant investment has been made toward the development of clinically relevant UT ligands for therapeutic intervention, but with little or no success to date. This system therefore remains to be therapeutically exploited. Pepducins and other lipidated peptides have been used as both mechanistic probes and potential therapeutics; therefore, pepducins derived from the human urotensin II receptor might represent unique tools to generate signaling bias and study hUT signaling networks. Two hUT-derived pepducins, derived from the second and the third intracellular loop of the receptor (hUT-Pep2 and [Trp
1 , Leu2 ]hUT-Pep3, respectively), were synthesized and pharmacologically characterized. Our results demonstrated that hUT-Pep2 and [Trp1 , Leu2 ]hUT-Pep3 acted as biased ago-allosteric modulators, triggered ERK1/2 phosphorylation and, to a lesser extent, IP1 production, and stimulated cell proliferation yet were devoid of contractile activity. Interestingly, both hUT-derived pepducins were able to modulate human urotensin II (hUII)- and urotensin II-related peptide (URP)-mediated contraction albeit to different extents. These new derivatives represent unique tools to reveal the intricacies of hUT signaling and also a novel avenue for the design of allosteric ligands selectively targeting hUT signaling potentially., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2021
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5. Functional Selectivity Revealed by N-Methylation Scanning of Human Urotensin II and Related Peptides.
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Merlino F, Billard É, Yousif AM, Di Maro S, Brancaccio D, Abate L, Carotenuto A, Bellavita R, d'Emmanuele di Villa Bianca R, Santicioli P, Marinelli L, Novellino E, Hébert TE, Lubell WD, Chatenet D, and Grieco P
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- Animals, CHO Cells, Cricetulus, HEK293 Cells, Humans, Intracellular Signaling Peptides and Proteins chemical synthesis, Intracellular Signaling Peptides and Proteins metabolism, Ligands, Male, Methylation, Nuclear Magnetic Resonance, Biomolecular, Peptide Hormones chemical synthesis, Peptide Hormones metabolism, Protein Conformation, Rats, Sprague-Dawley, Receptors, G-Protein-Coupled agonists, Receptors, G-Protein-Coupled metabolism, Urotensins chemical synthesis, Urotensins metabolism, Intracellular Signaling Peptides and Proteins pharmacology, Peptide Hormones pharmacology, Urotensins pharmacology
- Abstract
In accordance with their common but also divergent physiological actions, human urotensin II (1) and urotensin II-related peptide (2) could stabilize specific urotensin II receptor (UTR) conformations, thereby activating different signaling pathways, a feature referred to as biased agonism or functional selectivity. Sequential N-methylation of the amides in the conserved core sequence of 1, 2, and fragment U-II
4-11 (3) shed light on structural requirements involved in their functional selectivity. Thus, 18 N-methylated UTR ligands were synthesized and their biological profiles evaluated using in vitro competition binding assays, ex vivo rat aortic ring bioassays and BRET-based biosensor experiments. Biological activity diverged from that of the parent structures contingent on the location of amide methylation, indicating relevant hydrogen-bond interactions for the function of the endogenous peptides. Conformational analysis of selected N-methyl analogs indicated the importance of specific amide residues of 2 for the distinct pharmacology relative to 1 and 3.- Published
- 2019
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6. Urotensin core mimics that modulate the biological activity of urotensin-II related peptide but not urotensin-II.
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Strack M, Billard É, Chatenet D, and Lubell WD
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- Amides chemical synthesis, Amides chemistry, Molecular Conformation, Peptides, Cyclic chemistry, Urotensins chemistry, Peptides, Cyclic chemical synthesis, Urotensins chemical synthesis
- Abstract
A novel approach for the synthesis of head-to-tail cyclic peptides has been developed and used to prepare two mimics of the urotensin II-related peptide (URP) cyclic core. Mimics 1 and 2 (c[Trp-Lys-Tyr-Gly-ψ(triazole)-Gly] and c[Phe-Trp-Lys-Tyr-Gly-ψ(triazole)-Gly]) were respectively prepared using a combination of solid- and solution-phase synthesis. The silyl-based alkyne-modifying (SAM) linker enabled installation of C-terminal alkyne and N-terminal azide moieties onto linear peptide precursors, which underwent head-to-tail copper-catalyzed azide-alkyne cycloaddition (CuAAC) in solution. In an aortic ring contraction assay, neither 1 nor 2 exhibited agonist activity; however, both inhibited selectively URP- but not UII-mediated vasoconstriction. The core phenylalanine residue was shown to be important for enhancing modulatory activity of the urotensinergic system., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Published
- 2017
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7. Urotensin II((4-11)) Azasulfuryl Peptides: Synthesis and Biological Activity.
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Merlino F, Yousif AM, Billard É, Dufour-Gallant J, Turcotte S, Grieco P, Chatenet D, and Lubell WD
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- Animals, Aorta metabolism, CHO Cells, Cells, Cultured, Cricetulus, Humans, Male, Rats, Rats, Sprague-Dawley, Urotensins chemistry, Aorta drug effects, Urotensins chemical synthesis, Urotensins pharmacology
- Abstract
Cyclic azasulfuryl (As) peptide analogs of the urotensin II (UII, 1, H-Glu-Thr-Pro-Asp-c[Cys-Phe-Trp-Lys-Tyr-Cys]-Val-OH) fragment 4-11 were synthesized to explore the influences of backbone structure on biological activity. N-Aminosulfamides were inserted as surrogates of the Trp(7) and Lys(8) residues in the biologically relevant Trp-Lys-Tyr triad. A combination of solution- and solid-phase methods were used to prepare novel UII((4-11)) analogs 6-11 by routes featuring alkylation of azasulfuryl-glycine tripeptide precursors to install various side chains. The pharmacological profiles of derivatives 6-11 were tested in vitro using a competitive binding assay and ex vivo using a rat aortic ring bioassay. Although the analogs exhibited weak affinity for the urotensin II receptor (UT) without agonistic activity, azasulfuryl-UII((4-11)) derivatives 7-9 reduced up to 50% of the effects of UII and urotensin II-related peptide (URP) without affecting their potency.
- Published
- 2016
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8. Design of a peptidic inhibitor that targets the dimer interface of a prototypic galectin.
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Vladoiu MC, Labrie M, Létourneau M, Egesborg P, Gagné D, Billard É, Grosset AA, Doucet N, Chatenet D, and St-Pierre Y
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- Amino Acid Sequence, Amino Acid Substitution, Apoptosis drug effects, Blotting, Western, Galectins chemistry, Galectins genetics, Humans, Jurkat Cells, Models, Molecular, Peptides chemical synthesis, Protein Binding, Protein Structure, Quaternary, Recombinant Proteins chemistry, Recombinant Proteins metabolism, Recombinant Proteins pharmacology, Drug Design, Galectins antagonists & inhibitors, Peptides pharmacology, Protein Multimerization drug effects
- Abstract
Galectins are small soluble lectins that bind α-galactosides via their carbohydrate recognition domain (CRD). Their ability to dimerize is critical for the crosslinking of glycoprotein receptors and subsequent cellular signaling. This is particularly important in their immunomodulatory role via the induction of T-cell apoptosis. Because galectins play a central role in many pathologies, including cancer, they represent valuable therapeutic targets. At present, most inhibitors have been directed towards the CRD, a challenging task in terms of specificity given the high structural homology of the CRD among galectins. Such inhibitors are not effective at targeting CRD-independent functions of galectins. Here, we report a new class of galectin inhibitors that specifically binds human galectin-7 (hGal-7), disrupts the formation of homodimers, and inhibits the pro-apoptotic activity of hGal-7 on Jurkat T cells. In addition to representing a new means to achieve specificity when targeting galectins, such inhibitors provide a promising alternative to more conventional galectin inhibitors that target the CRD with soluble glycans or other small molecular weight allosteric inhibitors.
- Published
- 2015
- Full Text
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