Title :

Development of Receptor for Advanced Glycation End Products (RAGE) ligands through target directed dynamic combinatorial chemistry: a novel class of possible antagonists

Author(s) :

Dascalu, Anca‐elena [Auteur]
JUNIA [JUNIA]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Furman, Christophe [Auteur]
Landrieu, Isabelle [Auteur]
Cantrelle, François‐xavier [Auteur]
Mortelecque, Justine [Auteur]
Grolaux, Gaëlle [Auteur]
Gillery, Philippe [Auteur]
Tessier, Frédéric [Auteur]
Lipka, Emmanuelle [Auteur]
Billamboz, Muriel [Auteur]
JUNIA [JUNIA]
Boulanger, Eric [Auteur]
GHINET, ALINA [Auteur correspondant]
JUNIA [JUNIA]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]

Journal title :

Chemistry - a European Journal

Publisher :

Wiley-VCH Verlag

Publication date :

2024-02-20

ISSN :

0947-6539

HAL domain(s) :

Chimie

English abstract : [en]

Abstract RAGE is a transmembrane receptor of immunoglobulin family that can bind various endogenous and exogenous ligands, initiating the inflammatory downstream signaling pathways, including inflammaging. Therefore, RAGE ...
Show more >Abstract RAGE is a transmembrane receptor of immunoglobulin family that can bind various endogenous and exogenous ligands, initiating the inflammatory downstream signaling pathways, including inflammaging. Therefore, RAGE represents an attractive drug target for age‐related diseases. For the development of small‐molecule RAGE antagonists, we employed protein‐templated dynamic combinatorial chemistry (ptDCC) using RAGE′s VC1 domain as a template, the first application of this approach in the context of RAGE. The affinities of DCC hits were validated using microscale thermophoresis. Subsequent screening against AGE2 (glyceraldehyde‐modified AGE)‐sRAGE (solubleRAGE) (AGE2‐BSA/sRAGE) interaction using ELISA tests led to the identification of antagonists with micromolar potency. Our findings not only demonstrate the successful application of ptDCC on RAGE but also highlight its potential to address the pressing need for alternative strategies for the development of small‐molecule RAGE antagonists, an area of research that has experienced a slowdown in recent years.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

ANR Project :

Effets d'une exposition précoce et chronique aux AGE alimentaires sur l'inflammation chronique à bas bruit et les troubles liés à l'âge

Collections :

• Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167

Source :

Harvested from HAL