Identification of α2β1 integrin inhibitor VP-i with anti-platelet properties in the venom of Vipera palaestinae

Franziska T. Arlinghaus, Tatjana Momic, Narmeen Abu Ammar, Ela Shai, Galia Spectre, David Varon, Cezary Marcinkiewicz, Heinrich Heide, Philip Lazarovici, Johannes A. Eble*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Integrins are receptors of the extracellular matrix (ECM), playing a vital role in pathophysiological processes. They bind to ECM ligands like collagens and can mediate wound healing as well as tumor metastasis and thrombosis, thus being a part of cell adhesion and migration as well as platelet aggregation. For this reason, identifying α2β1 integrin-specific antagonists can assist in the development of drugs to treat tumor progression, angiogenesis, and cardiovascular diseases. Snake venoms have been shown to contain antagonists which target collagen-binding integrins. EMS16, rhodocetin, and VP12 are three toxins belonging to the C-type lectin-related protein family and have been proven to inhibit the α2β1 integrin, specifically the α2 integrin A domain.To specifically isolate antagonists targeting the α2β1 integrin A domain, we developed a protocol based on affinity chromatography. Using this novel approach, the toxin VP-i was isolated from Vipera palaestinae venom. We show that VP-i binds to the α2 integrin A domain and that it successfully inhibits adhesion of various cells to type I collagen as well as cell migration. Moreover, our results indicate that VP-i differs structurally from the previously purified VP12, although not functionally, and therefore is a further venom compound which can be utilized for drug development.

Original languageEnglish
Pages (from-to)96-105
Number of pages10
JournalToxicon
Volume64
DOIs
StatePublished - 5 Mar 2013
Externally publishedYes

Keywords

  • A domain
  • C-type lectin-related protein
  • Integrin α2β1
  • VP12

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