Metalloaminopeptidases of the Protozoan Parasite Plasmodium falciparum as Targets for the Discovery of Novel Antimalarial Drugs

Belinda  Mills; R. Elwyn  Isaac; Richard  Foster

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Metalloaminopeptidases of the Protozoan Parasite Plasmodium falciparum as Targets for the Discovery of Novel Antimalarial Drugs

机译：原生动物寄生虫疟原虫的金属氨基氨基肽作为发现新型抗疟药的目标

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Malaria poses a significant threat to approximately half of the world’s population with an annual death toll close to half a million. The emergence of resistance to front-line antimalarials in the most lethal human parasite species, Plasmodium falciparum (Pf ), threatens progress made in malaria control. The prospect of losing the efficacy of antimalarial drugs is driving the search for small molecules with new modes of action. Asexual reproduction of the parasite is critically dependent on the recycling of amino acids through catabolism of hemoglobin (Hb), which makes metalloaminopeptidases (MAPs) attractive targets for the development of new drugs. The Pf genome encodes eight MAPs, some of which have been found to be essential for parasite survival. In this article, we discuss the biological structure and function of each MAP within the Pf genome, along with the drug discovery efforts that have been undertaken to identify novel antimalarial candidates of therapeutic value.

机译：疟疾对全世界约一半人口构成重大威胁，每年死亡人数接近50万。在最致命的人类寄生虫物种恶性疟原虫（Pf）中出现对一线抗疟药物的耐药性，威胁着疟疾控制方面取得的进展。抗疟药物失去疗效的前景正在推动人们寻找具有新作用模式的小分子。寄生虫的无性繁殖严重依赖于通过血红蛋白（Hb）分解代谢的氨基酸循环，这使得金属氨肽酶（MAP）成为开发新药的诱人靶点。Pf基因组编码八个图谱，其中一些图谱对寄生虫的生存至关重要。在本文中，我们将讨论Pf基因组中每个图谱的生物结构和功能，以及为确定具有治疗价值的新型抗疟候选药物而进行的药物发现工作。

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《Journal of Medicinal Chemistry》 |2021年第4期|共23页
作者
Belinda Mills; R. Elwyn Isaac; Richard Foster;
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School of Chemistry University of Leeds;

School of Biology University of Leeds;

School of Chemistry University of Leeds;

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原文格式 PDF
正文语种 eng
中图分类药学;
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Metalloaminopeptidases of the Protozoan Parasite Plasmodium falciparum as Targets for the Discovery of Novel Antimalarial Drugs

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