The Mycobacterium tuberculosis MEP (2C-methyl-d-erythritol 4-phosphate) pathway as a new drug target.

The Mycobacterium tuberculosis MEP (2C-methyl-d-erythritol 4-phosphate) pathway as a new drug target.
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DOI:
10.1016/j.tube.2008.07.004
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发表时间:
2009-01
期刊:
Tuberculosis (Edinburgh, Scotland)
影响因子:
--
通讯作者:
Crick DC
Crick DC
中科院分区:
其他
文献类型:
--
作者:
Eoh H;Brennan PJ;Crick DC

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结核病(TB)仍然是一个主要的公共卫生问题,由于人类免疫缺陷病毒(HIV)-TB合并感染以及最近出现的多药耐药(MDR)和广泛耐药(XDR)-TB而变得更加复杂。迫切需要新型抗结核药物。在这种情况下,结核分枝杆菌的2C-甲基-D-MEP-磷酸(MEP)途径引起了人们的注意;它是结核分枝杆菌的几个重要途径之一。结核病的生存力和人类宿主缺乏同源酶。因此,MEP途径承诺细菌特异性药物靶标和鉴定不受基于靶标的毒性影响的先导化合物的潜力。事实上,现在已知磷咪霉素抑制MEP途径中的第二步。本文综述了M.结核病和这些如何可以在高通量筛选活动中进行操作,以寻找新的抗结核感染药物。
Tuberculosis (TB) is still a major public health problem, compounded by the human immunodeficiency virus (HIV)-TB co-infection and recent emergence of multidrug-resistant (MDR) and extensive drug resistant (XDR)-TB. Novel anti-TB drugs are urgently required. In this context, the 2C-methyl-D-erythritol 4-phosphate (MEP) pathway of Mycobacterium tuberculosis has drawn attention; it is one of several pathways vital for M. tuberculosis viability and the human host lacks homologous enzymes. Thus, the MEP pathway promises bacterium-specific drug targets and the potential for identification of lead compounds unencumbered by target-based toxicity. Indeed, fosmidomycin is now known to inhibit the second step in the MEP pathway. This review describes the cardinal features of the main enzymes of the MEP pathway in M. tuberculosis and how these can be manipulated in high throughput screening campaigns in the search for new anti-infectives against TB.
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