Complementary Peptides That Interfere with Platelet Aggregation and Adherence

Abstract

This article describes the application of the molecular recognition hypothesis to the critically important process of fibrinogen binding to platelets, a process that is the subject of extensive and intensive basic and clinical research. The objectives of the studies summarized below were to design, synthesize, and characterize peptides that can inhibit the binding of fibrinogen and related ligands to human platelets and thereby prevent platelet aggregation, adhesion, and clot retraction. The purpose of doing this work was twofold: first, to determine whether the molecular recognition hypothesis could serve as a useful rationale for the design of peptides that can specifically inhibit the binding of fibrinogen and related ligands to platelets; and second, to use these peptides to try to learn where fibrinogen binds to the platelet fibrinogen receptor. It was hoped that the results obtained not only would provide insight into platelet function but also might provide a rationale for the design of a clinically useful anti-thrombotic agent. Although our studies are not complete, they have resulted in the design of a variety of peptides that can inhibit platelet aggregation, adhesion, and clot retraction as a consequence of specifically inhibiting the binding of fibrinogen and related ligands to the platelet fibrinogen receptor. Although none of these peptides appears to be ligand specific, one or two of them may be specific for platelets .