Drug discovery research targeting the mechanism of peptide metabolism in sugar non-fermenting Gram-negative bacteria

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06071
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Iwate Medical University
• Principal Investigator: Sakamoto Yasumitsu 岩手医科大学, 薬学部, 教授 (00349036)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 薬剤耐性 / DPP / NFGNB / 糖悲発酵 / 歯周病 / 多剤耐性 / 微小重力

Outline of Final Research Achievements

In this research, we led to the development of antimicrobial agents with new mechanisms of action that contribute to the treatment of infections caused by certain multidrug-resistant bacteria. In collaboration with Kobe University, Niigata University, Nagaoka University of Technology, Kitasato University, JAXA, and others, we have been studying the crystal structure of target molecules and compound interactions required for SBDD, including the recognition mechanism of the S2 subsite of DPP7 from multidrug-resistant bacteria, which are sugar non-fermentative gram-negative bacteria that use peptides as a nutrient source. We have been conducting research on the crystal structure of target molecules and compound interactions required for SBDD. In this study, we advanced compound design by SBDD and succeeded in finding the compounds that inhibit the growth of certain multidrug-resistant bacteria and periodontal disease bacteria and patent application was filed.

Free Research Field

構造生物学

Academic Significance and Societal Importance of the Research Achievements

本研究開発により、ペプチドを栄養源とする糖非発酵性グラム陰性細菌に特有なペプチド分解酵素である
S46 DPPを標的とする阻害剤が実際に抗菌効果を示すことを証明できた。このことは、S46 DPPを有する多剤耐性菌や歯周病菌などの病原菌に対する新たな治療手段を提供し、薬剤耐性により既存抗菌薬が効かなくなった場合に必要となる新規作用機序の抗菌薬へと結びつく持続可能な社会を目ざすSDGsにとっても重要な成果である。