C-glyco"RGD" as αβ and αβ integrin ligands for imaging applications: Synthesis, in vitro evaluation and molecular modeling.
Fiche publication
Date publication
juillet 2019
Journal
Bioorganic & medicinal chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr KARCHER Gilles
Tous les auteurs :
Vucko T, Pétry N, Dehez F, Lambert A, Monari A, Lakomy C, Lacolley P, Regnault V, Collet C, Karcher G, Pellegrini-Moïse N, Lamandé-Langle S
Lien Pubmed
Résumé
The design of conjugates displaying simultaneously high selectivity and high affinity for different subtypes of integrins is a current challenge. The arginine-glycine-aspartic acid amino acid sequence (RGD) is one of the most efficient short peptides targeting these receptors. We report herein the development of linear and cyclic fluoro-C-glycoside"RGD" conjugates, taking advantage of the robustness and hydrophilicity of C-glycosides. As attested by in vitro evaluation, the design of these C-glyco"RGD" with a flexible three-carbon triazolyl linker allows distinct profiles towards αβ and αβ integrins. Molecular-dynamics simulations confirm the suitability of cyclic C-glyco-c(RGDfC) to target αβ integrin. These C-glyco"RGD" could become promising biological tools in particular for Positron Emission Tomography imaging.
Mots clés
C-Glycoside, Glycopeptide, Integrins, RGD
Référence
Bioorg. Med. Chem.. 2019 Jul 25;: