Development of Peptide Inhibitors to Block Type I and Type III Collagen-platelet Interaction

T.   M.   Chiang

Abstract

Platelet-collagen interaction plays an important role in hemostasis and pathological thrombosis. Upon an injury to the subendothelium of a blood vessel wall, platelets attach to the denuded substrate, aggregate, and release biological substances. Many investigators are trying to explore blocking agents to interrupt the adhesion of platelets to the damaged walls. To this date, extensive studies on developing inhibitors for platelet glycoprotein IIb / IIIa have been conducted. There are many trial reports showing that the efficacy of these antagonists has not completely blocked the adhesion of platelets to the distal site(s) of the injury. Type I and type III collagen are present in abundant amounts in blood vessel walls and other laboratories have obtained various active peptides from collagen molecules to block type I and type III collagen-platelet interaction. We have tried to develop active peptides from platelet receptors for types I and III collagen to aberrant both type I and type III collagen-induced platelet aggregation. We have defined effective and specific peptide inhibitors for each type of collagen to block binding to washed platelets, platelet aggregation, and adhesion of washed platelets to rabbit aortic segments.

Keywords: platelet aggregation inhibitor, platelet adhesion, collagen, peptide inhibitor, platelet collagen receptor, non-integrin receptor, platelet

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