Relationship Between the Binding Mode and the Activity of Stereoisomers of Beta-Lactamase Inhibitors

Journal of the Korean Chemical Society

Choonmi Kim¹  Insun Park¹  Inhee Choi¹  Sung Hee Mok¹ 

关键词: FlexiDock;    ¥â-Lactamase;    Inhibitor;    Stereoisomers;    Binding Modes;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

Using the computer docking program, FlexiDock, two sets of ¥á and ¥â isomers of novel allyl substituted derivatives of sulbactam were docked into ¥â-lactamase of Bacteroides fragilis and four diastereomers of 3-phenyl-clavams and four diastereomers of 6-methyl 3-phenyl clavams were docked into ¥â-lactamase of Enterobacter cloacae P99 to determine the binding modes of ¥â-lactamase-ligand complex. Isomers with high activities were docked stably inside the active sites with five hydrogen bonds whereas the others with low or no activities formed one to three hydrogen bonds or no bond at all, demonstrating the positive correlation between the binding modes and the activities. These results indicate that the biologically active stereoisomers can be selected by the binding mode differences through docking study. Thus, flexible docking used in this work could be a useful and effective method in the development of therapeutically effective stereoisomers of ¥â-lactamase inhibitors.

【 授权许可】

Unknown