Purification, synthesis and characterization of AaCtx, the first chlorotoxin-like peptide from Androctonus australis scorpion venom.

Ilhem Rjeibi (1) , Kamel Mabrouk (2) , Hend Mosrati (1) , Caroline Berenguer (3) , Hafedh Mejdoub (4) , Claude Villard (3) , Daniel Laffitte (3) , Denis Bertin (2) , L'Houcine Ouafik (3) , José Luis (3) , Mohamed Elayeb (1) , Najet Srairi-Abid (1)

1 Institut Pasteur de Tunis
2 LCP - Laboratoire Chimie Provence
3 CRO2 - Centre de Recherches en Oncologie biologique et Oncopharmacologie
4 USCR séquenceur de protéines

AaCtx is the first chlorotoxin-like peptide isolated from Androctonus australis scorpion venom. Its amino acid sequence shares 70% similarity with chlorotoxin from Leiurus quinquestriatus scorpion venom, from which it differs by twelve amino acids. Due to its very low concentration in venom (0.05%), AaCtx was chemically synthesized. Both native and synthetic AaCtx were active on invasion and migration of human glioma cells. However, their activity was found to be lower than that of chlorotoxin. The molecular model of AaCtx shows that most of amino acids differing between AaCtx and chlorotoxin are localized on the N-terminal loop and the α-helix. Based on known compounds that block chloride channels, we suggest that the absence of negative charged amino acids on AaCtx structure may be responsible for its weak activity on glioma cells migration and invasion. This finding serves as a starting point for structure-function relationship studies leading to design high specific anti-glioma drugs.

Domains: Chemical Sciences

Ilhem Rjeibi, Kamel Mabrouk, Hend Mosrati, Caroline Berenguer, Hafedh Mejdoub, et al.. Purification, synthesis and characterization of AaCtx, the first chlorotoxin-like peptide from Androctonus australis scorpion venom.. Molecular Ecology, 2011, 32 (4), pp.656-63. ⟨10.1016/j.peptides.2011.01.015⟩. ⟨pasteur-00606677⟩