The structure-antiaggregative activity relationship in a series of Arg-Gly-Asp analogues

A series of analogues of Arg-Gly-Asp tripeptide, the common structural element of most of the integrin receptor ligands, possessing different conformational features for the interaction with platelet receptors, were synthesized by the methods of conventional peptide chemistry for use in the search for antithrombotic agents. The distance between the guanidine group of Arg and the β-carboxyl group of Asp was shown to affect the antiaggregative activity. A potent inhibitor of platelet aggregation, tripeptide Arg-βAla-Asp, with IC₅₀ 10.6 = 10.6 μM (ADP, 1.5 μM) was revealed.