Inhibiting protein synthesis to treat malaria.
Inhibiting protein synthesis to treat malaria.
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抑制蛋白质合成来治疗疟疾。
DOI：
10.1126/science.abq4457
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Statsyuk,AlexanderV
中科院分区：
文献类型：
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作者：
Statsyuk,AlexanderV
尽管传统上由于担心毒性而避免使用，但由于共价药物的效力增强和药理作用延长，因此与靶蛋白不可逆地结合的共价药物重新引起了人们的兴趣。治疗疟疾的传统努力集中于开发具有自由基（青蒿素）和亲电子（镰刀菌蛋白酶抑制剂）作用机制的共价药物，但尚未开发亲核药物。在本期第 1074 页，Xieet al.() 鉴定了亲核前药 ML901，它抑制恶性疟原虫（一种引起疟疾的寄生虫）中的蛋白质合成，但不抑制人类细胞中的蛋白质合成，从而导致选择性毒性。
Although traditionally avoided because of fears about toxicity, there is a renewed interest in covalent drugs that irreversibly bond with target proteins owing to their enhanced potency and prolonged pharmacological effects. Traditional efforts to treat malaria have focused on developing covalent drugs with a radical (arteminisin) and electrophilic (falcipain inhibitors) mechanism of action, but nucleophilic drugs have not been pursued. On page 1074 of this issue, Xieet al.() identify the nucleophilic prodrug ML901, which inhibits protein synthesis inPlasmodium falciparum(a parasite that causes malaria) but not in human cells, leading to selective toxicity.