Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, 13, Place Pasteur, BP 74, 1002 Belvédère, Universités Tunis-El Manar, Tunisia.
Peptides. 2011 Apr;32(4):656-63. doi: 10.1016/j.peptides.2011.01.015. Epub 2011 Jan 22.
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.
AaCtx 是从澳大利亚红背蛛毒液中分离出的第一个氯毒素样肽。其氨基酸序列与来自 Leiurus quinquestriatus 蝎子毒液的氯毒素有 70%的相似性，不同之处在于有十二个氨基酸。由于其在毒液中的浓度非常低（0.05%），因此进行了 AaCtx 的化学合成。天然和合成的 AaCtx 都对人神经胶质瘤细胞的侵袭和迁移具有活性。然而，其活性被发现低于氯毒素。AaCtx 的分子模型表明，AaCtx 和氯毒素之间的大多数氨基酸差异位于 N 端环和α-螺旋上。基于已知的阻断氯离子通道的化合物，我们推测 AaCtx 结构上缺少带负电荷的氨基酸可能是导致其对神经胶质瘤细胞迁移和侵袭活性较弱的原因。这一发现为结构-功能关系的研究提供了起点，有助于设计针对神经胶质瘤的高特异性药物。
