Purification, synthesis and characterization of AaCtx, the first chlorotoxin-like peptide from Androctonus australis scorpion venom.
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.
Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, 13, Place Pasteur, BP 74, 1002 Belvédère, Universités Tunis-El Manar, Tunisia.
Ilhem
I
Rjeibi
Kamel
K
Mabrouk
Hend
H
Mosrati
Caroline
C
Berenguer
Hafedh
H
Mejdoub
Claude
C
Villard
Daniel
D
Laffitte
Denis
D
Bertin
L'Houcine
L
Ouafik
José
J
Luis
Mohamed
M
Elayeb
Najet
N
Srairi-Abid
D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification* / Q000633:toxicity; D012604:Scorpion Venoms / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D010455:Peptides; D012604:Scorpion Venoms; C091539:Chlorotoxin