Center for World Health and Medicine, Department of Molecular Microbiology, Saint Louis University, Saint Louis, MO 63104, USA.
Curr Top Med Chem. 2012;12(5):445-55. doi: 10.2174/156802612799362959.
Plasmepsins are the aspartic proteases of Plasmodium that play key roles in the survival of the parasite in its host. The plasmepsins of the digestive vacuole play an important role in hemoglobin degradation, providing the parasite with a vital source of nutrients. Recently, plasmepsin V has been shown to be an essential protease, processing hundreds of parasite proteins for export into the host erythrocyte. The functions of the remaining plasmepsins have yet to be discovered. Over the past decade, much effort has been placed towards developing plasmepsin inhibitors as antimalarial agents, particularly targeting the digestive vacuole. This review will highlight some of the recent work in this field with a particular focus on target druggability and strategies for identifying plasmepsins inhibitors as effective antimalarial drugs. Given recent advances in understanding the fundamental roles of the various plasmepsins, it is likely that the most effective antimalarial plasmepsin targets will be the non-digestive vacuole plasmepsins.
疟原虫的裂殖体蛋白酶是天冬氨酸蛋白酶，在寄生虫在宿主体内的存活中发挥着关键作用。消化液泡中的裂殖体蛋白酶在血红蛋白降解中发挥着重要作用，为寄生虫提供了重要的营养来源。最近，裂殖体蛋白酶 V 已被证明是一种必需的蛋白酶，它处理数百种寄生虫蛋白，将其输出到宿主红细胞中。其余裂殖体蛋白酶的功能尚未被发现。在过去的十年中，人们付出了巨大的努力来开发裂殖体蛋白酶抑制剂作为抗疟药物，特别是针对消化液泡。这篇综述将重点介绍该领域的一些最新工作，特别关注靶标可药性和识别裂殖体蛋白酶抑制剂作为有效抗疟药物的策略。鉴于最近在理解各种裂殖体蛋白酶的基本作用方面取得的进展，最有效的抗疟裂殖体蛋白酶靶标可能是非消化液泡裂殖体蛋白酶。
