Lebestatin, a disintegrin from Macrovipera venom, inhibits integrin-mediated cell adhesion, migration and angiogenesis.

Olfa Kallech-Ziri (1) , Luis José (2) , Salma Daoud (1) , Amine Bazaa (1) , Najet Srairi Abid (1) , Nicolas Andreotti (3) , Maxime Lehmann (2) , Raoudha Zouari (1) , Kamel Mabrouk (3) , Jacques Marvaldi (2) , Jean-Marc Sabatier (3) , Mohamed El Ayeb (1) , Naziha Marrakchi (1, 4)

1 Laboratoire des Venins et Toxines, Institut Pasteur de Tunis
2 Faculté de Pharmacie
3 Biochimie - Ingénierie des protéines
4 Faculté de médecine de Tunis

Lebestatin, a new member of the lysine-threonine-serine (KTS)-disintegrin family, was purified to homogeneity from Tunisian snake (Macrovipera lebetina) venom. It is a single-chain polypeptide composed of 41 amino acids. The amino-acid sequence of lebestatin shows that it displays a pattern of cysteines similar to other short disintegrins, but contains the sequence KTS rather than RGD in its integrin-binding loop. Lebestatin presents a high homology with obtustatin and viperistatin. Lebestatin interacts specifically with the alpha1beta1 integrin. It was thus able to inhibit both adhesion and migration of PC12 and alpha1beta1 integrin-expressing CHO cells (CHO-alpha1) to type I and IV collagens. This disintegrin also affected adhesion and migration of endothelial cells and exhibited an anti-angiogenic effect in vivo when using the 8-day-old embryo chick chorioallantoic membrane model.

Domaines: Sciences du Vivant [q-bio]

Olfa Kallech-Ziri, Luis José, Salma Daoud, Amine Bazaa, Najet Srairi Abid, et al.. Lebestatin, a disintegrin from Macrovipera venom, inhibits integrin-mediated cell adhesion, migration and angiogenesis.. Laboratory Investigation, 2005, 85 (12), pp.1507-16. ⟨10.1038/labinvest.3700350⟩. ⟨pasteur-00874069⟩