Enediol mimics as inhibitors of the D-arabinose 5-phosphate isomerase (KdsD) from Francisella tularensis.
Enediol mimics as inhibitors of the D-arabinose 5-phosphate isomerase (KdsD) from Francisella tularensis.
复制标题
Enediol 模拟土拉弗朗西斯菌 D-阿拉伯糖 5-磷酸异构酶 (KdsD) 的抑制剂。
DOI：
10.1016/j.bmcl.2010.12.066
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发表时间：
2011
影响因子：
2.7
通讯作者：
Woodard,RonaldW
中科院分区：
文献类型：
--
作者：
Yep,Alejandra;Sorenson,RoderickJ;Wilson,MichaelR;Showalter,HDHollis;Larsen,ScottD;Keller,PaulR;Woodard,RonaldW
我们探索了d-阿拉伯糖5-磷酸异构酶（KdsD，E. C. 5.3.1.13），其是一种高度传染性的革兰氏阴性病原体，作为潜在的生物武器引起了人们的关注，作为开发新型化疗药物的靶标。F.土拉热菌KdsD在大肠杆菌中由合成基因表达、纯化和表征。设计了一组异羟肟酸酯，模拟酶催化机制中的假定的酶中间体，并作为F.土拉菌最佳抑制剂的IC 50为7μM，是迄今报道的最有效的KdsD抑制剂。
We explored the d-arabinose 5-phosphate isomerase (KdsD, E.C. 5.3.1.13) from Francisella tularensis, a highly infectious Gram-negative pathogen that has raised concern as a potential bioweapon, as a target for the development of novel chemotherapeutics. F. tularensis KdsD was expressed in Escherichia coli from a synthetic gene, purified, and characterized. A group of hydroxamates designed to be mimics of the putative enediol intermediate in the enzyme’s catalytic mechanism were prepared and tested as inhibitors of F. tularensis KdsD. The best inhibitor, which has an IC50of 7μM, is the most potent KdsD inhibitor reported to date.