Possani Lourival D, Corona Miguel, Zurita Mario, Rodríguez Mario H
Departamento de Reconocimiento Molecular y Biología Estructural, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico.
Arch Med Res. 2002 Jul-Aug;33(4):398-404. doi: 10.1016/s0188-4409(02)00370-3.
Scorpion venom contains different types of peptides toxic to a variety of organisms whose molecular targets have been described as mainly ion-channels of excitable cells where they cause impairment of function. Based on mouse, cricket, and crustacean bioassays, specific toxins for each group of animals have been found. Chromatographic techniques were used to isolate and chemically characterize these peptides. One of the best-studied peptides is noxiustoxin, a 39-amino acid residue-long peptide specific for K(+)-channels. Hadrurin is another scorpion venom peptide whose activity was shown to be bactericidal to a variety of species. Structural similarities of a newly discovered peptide (scorpine) with those of defensins and cecropins showed that scorpion venom contains peptides toxic to microorganisms and malaria parasites. Scorpine was shown to disrupt the sporogonic development of Plasmodium berghei. Using this system as a model for malaria, we introduced the gene of scorpine into a vector for generation of transgenic flies resistant to the infection by Plasmodium. The final aim of this work is to incorporate this gene under the promoter of proteolytic enzymes of digestive tract of mosquitoes for synthesis and liberation of toxic peptide(s) into stomach of freshly fed mosquitoes potentially carrying Plasmodium gametes. In this manner, a putative transgenic mosquito with these characteristics would secrete a toxic peptide with digestive enzymes into midgut, impairing proper development of Plasmodium, hence controlling malaria, one of the most important tropical diseases worldwide.
蝎毒含有不同类型的肽，这些肽对多种生物有毒，其分子靶点主要被描述为可兴奋细胞的离子通道，在这些通道中它们会导致功能受损。基于小鼠、蟋蟀和甲壳类生物测定，已发现针对每组动物的特定毒素。采用色谱技术分离并对这些肽进行化学表征。研究得最透彻的肽之一是noxius毒素，它是一种对钾通道具有特异性的39个氨基酸残基长的肽。Hadrurin是另一种蝎毒肽，其活性已被证明对多种物种具有杀菌作用。新发现的肽（scorpine）与防御素和杀菌肽的结构相似性表明，蝎毒含有对微生物和疟原虫有毒的肽。已证明scorpine会破坏伯氏疟原虫的孢子生殖发育。以该系统作为疟疾模型，我们将scorpine基因导入载体，以产生对疟原虫感染具有抗性的转基因果蝇。这项工作的最终目标是将该基因整合到蚊子消化道蛋白水解酶的启动子下，以便在刚进食的可能携带疟原虫配子的蚊子胃中合成并释放有毒肽。通过这种方式，具有这些特征的推定转基因蚊子会将有毒肽与消化酶一起分泌到中肠，损害疟原虫的正常发育，从而控制疟疾，这是全球最重要的热带疾病之一。
