The Structure--Antiaggregative Activity Relationship in a Series of Arg-Gly-Asp Analogues
O. V. Mel'nik , # V. P. Martinovich , and V. P. Golubovich
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Institute of Bioorganic Chemistry , National Academy of Sciences of Belarus , ul. akademika Kuprevicha 5/2, Minsk, 220141 Belarus
Received August 5, 2005; in final form, October 10, 2005
Abstract: 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-@[beta]@Ala-Asp, with IC50 = 10.6 μM (ADP, 1.5 μM), was revealed.
Key words: Arg-Gly-Asp peptide, peptide synthesis, platelet aggregation
Russian Journal of Bioorganic Chemistry 2006, 32 (2):122-128