RGDS AND LGGAKQAGDV BINDING SITES ON GPIIB/IIIA

该项目的目的是鉴定氨基酸

The objective of this project is to identify the amino acid sequence(s) of the region(s) of the fibrinogen receptor (the glycoprotein IIb/IIIa complex) which bind peptides corresponding to the RGDS and LGGAKQAGDV sequences, respectively, of the alpha and gamma-chains of Fg. This will be accomplished by using the molecular recognition hypothesis and the cDNA sequence information for the alpha and gamma-chains of human fibrinogen. This information will be used to direct the synthesis of peptides which are presumptive analogues of the fibrinogen binding region(s) of its receptors. These presumptive peptide analogues of the fibrinogen receptor are expected to be complementary with the peptides RGDS and LGGAKQAGDV and therefore be able to bind fibrinogen. This expectation will be tested by determining if these peptides can inhibit platelet aggregation, fibrinogen binding and clot retraction. Active peptides will also be characterized by affinity chromatography and equilibrium dialysis. Immunological techniques will be used to determine if the presumptive fibrinogen receptor analogues have epitopes which are present on platelet fibrinogen receptors. This approach will be extended to the other adhesive glycoproteins which can bind to GPIIb/IIIa complexes: fibronectin, vitronectin and von Willebrand factor. Identification of the ligand binding region(s) of the fibrinogen receptors will increase our understanding of platelet function and thereby provide information useful for the control of thrombotic disease. Specifically, characterization of the peptide analogues of the fibrinogen receptors which inhibit platelet aggregation, clot retraction and fibrinogen binding may provide a rationale for the design of clinically useful anti-thrombotic agents.