Expression Of Adinbitor In Pichia Pastoris, A Disintegrin From The Snake Venom Of Agkistrodon Halys Brevicaudus Stejneger, And Characterization Of Its Biologic Activities

Disintegrins are a family of small proteins mainly derived from snake venoms. Most of the disintegrins contain RGD or KGD sequence which is the structural motif recognized by the platelet fibrinogen receptorαIIbβ3, and also act as potent antagonists of several integrins includingαVβ3 andα5β1 which are expressed on vascular endothelial cells and some tumor cells. In addition to their potential antiplatelet activity, studies of disintegrins such as Rhodostomin, Accutin, Salmosin, Saxatilinand Contortrostatin etc., have revealed a new application in inhibiting angiogenesis and tumor growth .Because disintegrins can inhibit the binding of ECM to integrins according to the RGD or KGD sequence, their signaling pathways are close related with integrins'pathways.Integrins are a family of heterodimeric receptors on cell surface. The known 18αand 8βsubunits combine to form at least 24αβheterodimers. Most cells express more than one type of integrin heterodimer. Integrin expression profiles are unique for distinct cell types, and change with development stage and physiological conditions within a cell type. The common binding site of ligands is composed of the N-terminal ofαandβsubunits. Because most of cell integrins recognize RGD sequence and most of ECM molecules contain the sequence RGD, the RGD sequence has been already considered as the binding site of ECM molecules to integrins . Although the intracellular part of integrins is much shorter, they can form links to the cytoskeleton throughα-actinin, talin and vinculin.