Novel Small Molecule Inhibitors of MDR Mycobacterium tuberculosis by NMR Fragment Screening of Antigen 85C
Novel Small Molecule Inhibitors of MDR Mycobacterium tuberculosis by NMR Fragment Screening of Antigen 85C
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DOI：
10.1021/jm100993z
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发表时间：
2010-12-09
影响因子：
7.3
通讯作者：
Schade, Markus
中科院分区：
文献类型：
--
作者：
Scheich, Christoph;Puetter, Vera;Schade, Markus
尽管基因组信息丰富，但基于蛋白质靶点的新型抗生素的发现在很大程度上是不成功的。尤其需要的是治疗结核病的新抗生素，结核病每年导致160万人死亡，多重耐药病例迅速增加。通过将基于片段的药物发现与早期全细胞抗菌筛选相结合，我们发现了新的耐多药结核分枝杆菌（Mtb）配体高效抑制剂，该抑制剂与结核分枝杆菌蛋白抗原85C的底物位点结合，迄今未在结核分枝杆菌化疗中使用。
Protein target-based discovery of novel antibiotics has been largely unsuccessful despite rich genome information. Particularly in need are new antibiotics for tuberculosis, which kills 1.6 million people annually and shows a rapid increase in multiple-drug-resistant cases. By combining fragment-based drug discovery with early whole cell antibacterial screening, we discovered novel ligand-efficient inhibitors of multiple-drug resistant Mycobacterium tuberculosis (Mtb), which bind to the substrate site of the Mtb protein antigen 85C, hitherto unused in Mtb chemotherapy.