一种多阶段的抗疟疾药物向了入侵和退出所必需的等离子素IX和X
Paco Pino1, Reto Caldelari2, Budhaditya Mukherjee3
1Department of Microbiology and Molecular Medicine, Faculty of Medicine-University of Geneva, Centre Médical Universitaire (CMU), 1211 Geneva, Switzerland. paco.pino@unige.ch dominique.soldati-favre@unige.ch.
Science (New York, N.Y.)
|October 28, 2017
概括
一种新型化合物49c抑制了疟疾寄生虫入侵和退出所必需的关键蛋白酶 (等离子素IX和X). 这种多阶段抗菌活性为抗疟疾提供了潜在的新疗法.
科学领域:
- 疟疾学
- 寄生虫学
- 蛋白酶抑制剂药物发现
背景情况:
- 对于疟疾寄生虫 (Plasmodium) 的入侵和退出来说,分泌器官细胞的调节是至关重要的.
- 许多Plasmodium效应蛋白在外细胞化前后经历必要的蛋白质分解处理.
研究的目的:
- 研究一种基于基乙胺的新型支架化合物的抗质活性, 49c.
- 为了确定化合物49c是否针对参与Plasmodium分泌蛋白的前细胞处理的蛋白质.
主要方法:
- 评估了化合物49c的多阶段抗血活性.
- 研究的化合物49c抑制了等离子素IX (PMIX) 和X (PMX) 的活性.
- 使用条件基因切除来研究PMIX在寄生虫入侵中的作用.
主要成果:
- 化合物49c表现出多个阶段的抗血活性.
- 化合物49c通过向PMIX和PMX来抑制rhoptry和microneme蛋白的前细胞处理.
- 条件切除PMIX证实它在寄生虫入侵中的重要作用.
- 再组合的PMIX和PMX被证明对49c化合物具有敏感性的分裂入侵和退出因子.
结论:
- 化合物49c是PMIX和PMX的强有力的抑制剂,这是Plasmodium中关键的酸蛋白酶.
- 用像49c这样的抑制剂向PMIX和PMX是开发新抗疟疾药物的有希望的策略.
- 这项研究强调了前细胞蛋白处理对疟疾寄生虫传染性的重要性.
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