KTS and RTS-Disintegrins: Anti-Angiogenic Viper Venom Peptides Specifically Targeting the α1β 1 Integrin

Integrins α1β1 and α2β1 are highly expressed on the microvascular endothelial cells, and blocking of their adhesive properties significantly reduced the VEGF-driven neovascularization ratio and tumor growth in animal models. Hence, inhibitors of the α1β1 and α2β1 integrins, alone or in combination with antagonists of other integrins involved in angiogenesis (eg. αvβ3, αvβ5, and α6β4), may prove benefitial in the control of tumor neovascularization. Viperidae snakes have developed in their venoms an efficient arsenal of integrin receptor antagonists. KTS- (obtustatin, viperistatin, lebestatin) and RTS- (jerdostatin) disintegrins represent viper venom peptides that specifically block the interaction of the α1β1 integrin with collagens IV and I in vitro and angiogenesis in vivo. The possible therapeutic approach towards tumor neovascularization by targeting the α5β1, αvβ5 and αvβ3 integrins with RGD-bearing disintegrins has been explored in a number of laboratories. Here we discuss structure-function correlations of the novel group of specific (K/R)TS-disintegrins targeting the α1β1 integrin. Keywords: extracellular matrix, integrin inhibitor, synthetic RGD peptides, obtustatin, viperistatin