Peptide mimics of glycosaminoglycans : synthesis, structures and biological activities ; Mimes peptidiques de glycosaminoglycanes : synthèses, structures et activités biologiques
| Title: | Peptide mimics of glycosaminoglycans : synthesis, structures and biological activities ; Mimes peptidiques de glycosaminoglycanes : synthèses, structures et activités biologiques |
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| Authors: | Marquant, Rodrigue |
| Contributors: | 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 - CNRS Chimie (INC-CNRS)-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 - CNRS Chimie (INC-CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - 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)-Centre National de la Recherche Scientifique (CNRS); Sorbonne Université; Jean-Maurice Mallet; Solange Lavielle |
| Source: | https://theses.hal.science/tel-03905719 ; Chimie organique. Sorbonne Université, 2021. Français. ⟨NNT : 2021SORUS305⟩. |
| Publisher Information: | CCSD |
| Publication Year: | 2021 |
| Subject Terms: | Mimics; Biacore; Homeodomain; Otx2; Sulfopeptides; Glycosaminoglycans; RMN; Homéodomaine; Mimes; Glycosaminoglycanes; [CHIM.ORGA]Chemical Sciences/Organic chemistry; [SDV.BBM]Life Sciences [q-bio]/Biochemistry; Molecular Biology |
| Description: | Glycosaminoglycans (GAGs) are linear polysaccharides, more or less sulfated, present on the surface of cells and in the extracellular matrix. They interact with a large number of proteins (cytokines, growth factors, enzymes, etc.) and are involved in various physiological and pathological processes. As part of my thesis work, we designed and synthesized GAGs mimetic molecules: anionic peptides of 12 to 24 amino acids, carrying repeated motifs (EC'AC ')n and exhibiting the characteristic functions of natural GAGs, namely the acid functions, provided by glutamic acid, and sulfonic functions, obtained by oxidation of cysteines. A first generation of these sulfopeptides was studied, at the Collège de France, as inhibitors of the interaction of a homeodomain protein (Otx2) with the network of GAGs present around a target cell type of this protein. The peptide comprising six "EC'AC" motifs has shown very promising in vivo activity. A structural study by NMR was then carried out to analyze the interactions of these sulfopeptides with the Otx2 protein produced with a double 13C, 15N labeling. This study confirmed that the interaction takes place at the GAG binding domain of the protein. This interaction also affects the homeodomain helix 3, which is responsible for the internalization of Otx2 into cells. Finally, we completed this structural study with a Biacore-type approach, to develop a strategy for faster analysis of the activity of our analogues and allow us to develop an efficient structure-activity study. ; Les Glycosaminoglycanes (GAGs) sont des polysaccharides linéaires, plus ou moins sulfatés, présents à la surface des cellules et dans la matrice extracellulaire. Ils interagissent avec un grand nombre de protéines (cytokines, facteurs de croissance, enzymes .) et sont impliqués dans divers processus physiologiques et pathologiques. Dans le cadre de mon travail de thèse, nous avons conçu et synthétisé des molécules mimes de GAGs : des peptides anioniques de 12 à 24 acides aminés, portant des motifs répétés de ... |
| Document Type: | doctoral or postdoctoral thesis |
| Language: | French |
| Relation: | NNT: 2021SORUS305 |
| Availability: | https://theses.hal.science/tel-03905719; https://theses.hal.science/tel-03905719v1/document; https://theses.hal.science/tel-03905719v1/file/MARQUANT_Rodrigue_2021.pdf |
| Rights: | https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: | edsbas.4C2FA7DF |
| Database: | BASE |