KTS and RTS-disintegrins: anti-angiogenic viper venom peptides specifically targeting the alpha 1 beta 1 integrin.

Abstract:

:Integrins alpha(1)beta(1) and alpha(2)beta(1) 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 alpha(1)beta(1) and alpha(2) beta(1) integrins, alone or in combination with antagonists of other integrins involved in angiogenesis (eg. alpha (v)beta(3), alpha(v)beta(5), and alpha(6)beta(4)), may prove beneficial 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 alpha(1)beta (1) integrin with collagens IV and I in vitro and angiogenesis in vivo. The possible therapeutic approach towards tumor neovascularization by targeting the alpha (5)beta (1), alpha(v)beta(5) and alpha (v)beta(3) 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 alpha(1)beta(1) integrin.

journal_name

Curr Pharm Des

authors

Calvete JJ,Marcinkiewicz C,Sanz L

doi

10.2174/138161207782023766

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

2853-9

issue

28

eissn

1381-6128

issn

1873-4286

journal_volume

13

pub_type

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