Nonphosphate inhibitors of IspE protein, a kinase in the non-mevalonate pathway for isoprenoid biosynthesis and a potential target for antirnalarial therapy
Nonphosphate inhibitors of IspE protein, a kinase in the non-mevalonate pathway for isoprenoid biosynthesis and a potential target for antirnalarial therapy
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DOI：
10.1002/cmdc.200700014
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发表时间：
2007-06-01
期刊：
影响因子：
3.4
通讯作者：
Diederich, Francois
中科院分区：
文献类型：
--
作者：
Hirsch, Anna K. H.;Lauw, Susan;Diederich, Francois
The discovery of the non-mevalonate pathway for the biosynthesis of the isoprenoid precursors isopentenyl diphosphate (IPP, 1) and dimethylallyl diphosphate (DMAPP, 2) in the 1990s opened the way for new approaches in the fight against infectious diseases. This pathway starts with the condensation of pyruvate 3 and glyceraldehyde 3-phosphate 4 and is used exclusively by pathogenic bacteria such as Mycobacterium tuberculosis, and by the protozoan Plasmodium parasites (Scheme 1).[1] Mammals, on the other hand, use the alternative mevalonate pathway. Hence, the development of small-molecule inhibitors for the enzymes of the nonmevalonate pathway constitutes a novel approach in the treatment of important infectious diseases.[2]Malaria is without a doubt the most important and devastating tropical disease with 300–500 million clinical cases and between one and three million deaths a year. In light of the emergence of drug and insecticide resistance, the need for medicines with a novel mode of action is ever increasing.[3]
