title: Identification of α2β1 integrin inhibitor VP-i with anti-platelet properties in the venom of Vipera palaestinae.
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.
authors: Center for Molecular Medicine, Department of Vascular Matrix Biology, Frankfurt University Hospital, Excellence Cluster Cardio-Pulmonary System, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. arlinghaus@med.uni-frankfurt.de
authors: Franziska T
authors: FT
authors: Arlinghaus
authors: Tatjana
authors: T
authors: Momic
authors: Narmeen Abu
authors: NA
authors: Ammar
authors: Ela
authors: E
authors: Shai
authors: Galia
authors: G
authors: Spectre
authors: David
authors: D
authors: Varon
authors: Cezary
authors: C
authors: Marcinkiewicz
authors: Heinrich
authors: H
authors: Heide
authors: Philip
authors: P
authors: Lazarovici
authors: Johannes A
authors: JA
authors: Eble
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005354:Fibrosarcoma / Q000188:drug therapy; D006801:Humans; D038982:Integrin alpha2beta1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D014757:Viper Venoms / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D017819:Viperidae / Q000378:metabolism*
chemical_list: D038982:Integrin alpha2beta1; D010975:Platelet Aggregation Inhibitors; D014757:Viper Venoms