Development of Inhibitors for Metallo-beta-lactamases

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08458
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including mycology)
• Research Institution: Chiba University
• Principal Investigator: Hoshino Tyuji 千葉大学, 大学院薬学研究院, 准教授 (90257220)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 阻害化合物 / 薬剤耐性菌 / メタロβ-ラクタマーゼ / 理論薬物設計 / 有機合成 / X線結晶構造解析 / 酵素活性阻害 / 構造活性相関

Outline of Final Research Achievements

Beta-lactamase is one kind of enzymes which dissociate beta-lactam antibiotics such as penicillin and imipenem. Many bacteria that are resistant to antibiotics carry the genome of beta-lactamase and generate it for drug-resistance. In this study, we focused on the metallo-beta-lactamase that is high enzymatic activity among several types of beta-lactamases. As a consequence of the in silico and in vitro chemical screening, we identified three chemical compounds that block the action of metallo-beta-lactamase. Two of them were synthesized in our study and utilized as a fundamental skeleton of further chemical modification. The other one was purchased from a supplier. We successfully obtained the binding structure between metallo-beta-lactamase and one of the identified compounds. The information of the binding structure will be important for the rational design of the chemicals that have high inhibitory potency.

Free Research Field

物理化学