A Potent Integrin Antagonist from a Small Library of Cyclic RGD Pentapeptide Mimics Including Benzyl-Substituted Azabicycloalkane Amino Acids

A small library of cyclic RGD pentapeptide mimics, including benzyl‐substituted azabicycloalkane amino acids, was synthesized with the aim of developing active and selective integrin antagonists. In vitro binding assays established one particular compound with affinity for both the αvβ3 and the αvβ5 integrins. The synthesis in solution and the in vitro screening of these RGD derivatives, as well as the determination of the conformational properties of the integrin ligands by spectroscopic and computational methods are described. Vitronectin receptors αvβ3 and αvβ5 have received increasing attention as therapeutic targets because of their critical role in tumor‐induced angiogenesis and formation of metastasis. A new potent integrin antagonist was synthesized, and herein we describe the solution‐phase synthesis, in vitro screening, and determination of the conformational properties of the integrin ligands by spectroscopic and computational methods.