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首页> 外文期刊>Journal of enzyme inhibition and medicinal chemistry. >Kinetic characterization of a slow-binding inhibitor of Bla2: thiomaltol
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Kinetic characterization of a slow-binding inhibitor of Bla2: thiomaltol

机译:慢结合抑制剂Bla2的动力学表征:麦芽糖醇

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The increasing prevalence of drug resistant bacteria is a pandemic problem. Metallo-beta-lactamases (MBLs) are one of the main causes of drug resistance due to hydrolysis of (3-lactam antibiotics. Thus, the development of effective inhibitors of MBLs remains urgent. The compound thiomaltol was used as a lead compound to investigate its ability to inhibit metallo-beta-lactamase from Bacillus anthracis (Bla2), which causes anthrax. Kinetic evaluation with nitrocefin as a substrate indicates that thiomaltol inhibits Bla2 in a time-dependent manner with an IC50 value of 290 mM after 20 min preincubation. Progress curve analysis and reversibility tests suggest that thiomaltol is a reversible, slow-binding inhibitor with a K of 85(+-)30 u.M. Furthermore, studies on the modality of inhibition and in silico analysis indicate thiomaltol to be a competitive inhibitor. The results demonstrate that thiomaltol is a promising lead compound for slow binding inhibitor design of Bla2.
机译:耐药菌的流行是大流行病。金属β-内酰胺酶(MBLs)是由于(3-内酰胺类抗生素)水解而引起耐药性的主要原因之一,因此,迫切需要开发有效的MBL抑制剂。化合物硫代麦芽酚被用作主要化合物进行研究以硝基cefin为底物进行的动力学评估表明,硫代麦芽酚以时间依赖性方式抑制Bla2,其IC50值为290 mM,在孵育50分钟后,IC50值为290 mM。进度曲线分析和可逆性测试表明,硫代麦芽酚是可逆的慢结合抑制剂,K值为85(+-)30 uM。此外,对抑制方式和计算机分析的研究表明,硫代麦芽酚是一种竞争性抑制剂。证明硫代麦芽酚是用于Bla2慢结合抑制剂设计的有前途的先导化合物。

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