Structure Function Relationships of KTS Disintegrins and Design of Antiangiogenic Drugs

Author(s): Olfa Kallech-Ziri, Jose Luis, Ziad Faljoun, Jean-Marc Sabatier, Maxime Lehmann, Mohamed El Ayeb, Naziha Marrakchi, Erwann Loret

Journal Name: Letters in Drug Design & Discovery

Volume 7 , Issue 1 , 2010

Become EABM
Become Reviewer
Call for Editor


Disintegrins are natural toxins found in snake venom having anti angiogenic activity. The KTS disintegrins group appears to be the most interesting as specific blocking agent of tumor growth. We report the chemical synthesis of three KTS disintegrins (Lebestatin, Obtustatin and Viperistatin) carried out with different substitution. The activity of these synthetic peptides (41 aa) and native Lebestatin purified from venom was compared with cell adhesion and migration assays. Synthetic and native Lebestatin inhibit cell adhesion of PC12 cells at 0.2 nM and integrin-dependent migration of CHO cells at 1 nM. This study shows that Lebestatin has the highest activity followed by Obtustatin and then Viperistatin in the two assays. Circular dichroism spectra of these KTS disintegrins show that their folding is similar. Molecular modeling shows that two arginines (8 and 24) and two lysines (21 and 32) have probably their chemical function interacting with integrins in protruding from the surface of Lebestatin. This study should help to design a lead compound to discover a new family of anti-angiogenic drugs.

promotion: free to download

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2010
Page: [36 - 40]
Pages: 5
DOI: 10.2174/157018010789869325

Article Metrics

PDF: 15