C-glyco"RGD" as α IIb β 3 and α v β integrin ligands for imaging applications: Synthesis, in vitro evaluation and molecular modeling.

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 α _IIb β ₃ and α _v β ₃ integrins. Molecular-dynamics simulations confirm the suitability of cyclic C-glyco-c(RGDfC) to target α _v β ₃ integrin. These C-glyco"RGD" could become promising biological tools in particular for Positron Emission Tomography imaging.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)