The University of Queensland, School of Chemistry and Molecular Biosciences, Brisbane, QLD 4072, Australia.
Bioorg Med Chem Lett. 2011 Jun 1;21(11):3282-5. doi: 10.1016/j.bmcl.2011.04.027. Epub 2011 Apr 13.
The emergence of metallo-β-lactamases (MBLs) capable of hydrolysing a broad spectrum of β-lactam antibiotics is particularly concerning for the future treatment of bacterial infections. This work describes the discovery of lead compounds for the development of new inhibitors using a competitive colorimetric assay based on the chromogenic cephalosporin CENTA, and a 500 compound Maybridge™ library suitable for fragment-based screening. The interactions between identified inhibitory fragments and the active site of the MBL from Klebsiella pneumoniae and Pseudomonas aeruginosa were probed by in silico docking studies.
金属β-内酰胺酶（MBLs）的出现能够水解广泛的β-内酰胺抗生素，这对未来细菌感染的治疗尤其令人担忧。本工作描述了使用基于显色头孢菌素CENTA 的竞争性比色测定法和适用于片段筛选的 500 种 Maybridge™文库，发现用于开发新抑制剂的先导化合物的情况。通过计算机对接研究探测了在克雷伯氏肺炎菌和铜绿假单胞菌的 MBL 的活性部位与鉴定出的抑制性片段之间的相互作用。
