Synthesis, SAR and in vitro evaluation of new cyclic Arg-Gly-Asp pseudopentapeptides containing a s-cis peptide bond as integrin αvβ3 and αvβ5 ligands

摘要: Abstract The solid-phase synthesis of two diastereomeric cyclic pseudopeptides containing the Arg-Gly-Asp sequence and dipeptide isostere 2-amino-3-oxotetrahydro-1 H -pyrrolizine-7a(5 )-carboxylic acid (GPTM) is described. Competition binding assays to purified α v β 3 5 integrins with respect [ 125 I]echistatin showed a high inhibitory activity for (2 S ,7a )-GPTM derivative. Effects structural constraint induced by enantiomeric scaffolds R on conformation have been computationally investigated using as reference recently solved X-ray structure cyclo(Arg-Gly-Asp- d -Phe-[ N -Me]Val) in complex extracellular fragment receptor. computational method disclosed key role played bridging water molecule differentiating ligands diverse stabilization ligand–protein complex.