Biochemical analysis of the molecular mechanism of action of natural integrin inhibitors

摘要

Disintegrins are a family of platelet aggregation inhibitors found in snake venoms (Gould et al., 1990). They are short soluble peptides (47-84 aminoacids) that bind platelet integrin alpha_(IIb)beta_3, thereby preventing binding to fibrinogen and hence platelet aggregation. Disintegrins are potential antithrombotic agents: they have been shown to accelerate thrombolysis and prevent reocclusion in in vivo coronary thrombosis model systems (Kaku et al, 1997; Lee et al., 1999). Disintegrins also bind other integrins on fibroblast, osteoclast and melanoma cells (Huang, 1998), thus preventing these cells from adhering to extracellular matrix (ECM) components.