Peptides derived from platelet non-integrin collagen-receptors or types I and III collagen inhibit collagen-platelet interaction.
Platelet-collagen interaction plays an important role in hemostasis and pathological thrombosis. Upon an injury to the subendothelium of a blood vessel wall, platelets adhere to the denuded substrate, aggregate, and release biological substances. Many investigators have explored the use of blocking agents to interrupt the final step of binding fibrinogen on glycoprotein (GP) IIb/IIIa of activated platelets. A potent peptide is Arg-Gly-Asp-Ser (RGDS) and its derivatives in various forms. Results from many clinical trials show that the efficacy of these antagonists does not lie in blocking the adhesion of platelets to the distal site(s) of the injury as expected. Because type I and type III collagens are predominant components of blood vessel walls, other laboratories and ours have defined various active peptides from either collagen molecules or platelets as useful for blocking collagen-platelet interaction. An active hybrid peptide derived from both platelet types I and type III collagen receptors that abolishes type I and type III collagen-induced platelet aggregation has been obtained. The hybrid peptide inhibits the binding of type I and type III collagens to washed human platelets, platelet aggregation, and the adhesion of washed platelets to rabbit aortic segments. However, the usefulness of the defined hybrid peptide in preventing thrombi formation in vivo requires further investigation.
Chiang
Thomas M
TM
Department of Veterans Affairs, University of Tennessee Health Science Center, Memphis, TN 38104, USA. tchiang@utmem.edu
Zhu
J
J
Woo-Rasberry
Virginia
V
D000818:Animals; D001792:Blood Platelets / Q000737:chemistry* / Q000187:drug effects*; D003094:Collagen / Q000037:antagonists & inhibitors*; D024042:Collagen Type I / Q000737:chemistry*; D024043:Collagen Type II / Q000737:chemistry*; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D038981:Receptors, Collagen / Q000737:chemistry*
D024042:Collagen Type I; D024043:Collagen Type II; D010455:Peptides; D038981:Receptors, Collagen; D003094:Collagen