The discovery of disintegrins

Abstract

Disintegrins represent a class of low molecular weight, Arg-Gly-Asp(RGD)/Lys-Gly-Asp(KGD)-containing, cysteine-rich polypeptides derived from venoms of various viper snakes. They bind to various integrins (e.g. αIIbβ3, αvβ3, α5β1 and others) expressed on cell membrane surface, with various degrees of affinity and specificity. Disintegrins were originally discovered as antiplatelet agents by acting as platelet membrane αIIbβ3 antagonists. However, they also have been found to bind αvβ3, α5β1 or α4β1 expressed on endothelial cells, fibroblasts, phagocytes, and tumor cells, thus affecting cell-matrix and cell-cell interaction. The homologous molecular structure among disintegrin, snake venom metalloproteinase (SVMP), and ADAM (a disintegrin and metalloproteinase) reveals their evolutionary relationship. Based on the structure-activity relationship of these molecules and integrins, the potential applications of these disintegrins and their derivatives are briefly discussed in field of arterial thrombosis, cell adhesion, cell migration, angiogenesis, inflammation, and tumor metastasis.