Multi-component linking strategy for the natural product drug discovery.

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15241
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
• Research Institution: Hokkaido University
• Principal Investigator: Katsuyama Akira 北海道大学, 薬学研究院, 助教 (20824709)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 創薬化学 / ペプチド / 構造最適化 / ペプチドスキャニング

Outline of Final Research Achievements

As structural modification of natural products with complex structures is labour intensive, there is a need to improve the efficiency of this step. The primary objective of this study was to develop a multi-component linking strategy for structural optimization of peptide-based natural products. This method allows the introduction of multiple chemical modifications in natural products. To demonstrate the efficacy of this method, the antimicrobial natural product polymyxin B was used in this study. Using a serine-threonine ligation (STL), a number of derivatives were synthesised comprehensively and successfully modified for antimicrobial activity.

Free Research Field

創薬化学

Academic Significance and Societal Importance of the Research Achievements

細菌による感染症は、現代の公衆衛生においても再び脅威となりつつあるが、どのような感染症が流行するかを事前に予測し、それに対して適切な抗菌薬を開発するのは困難である。こうした疾患に対しては、多数の性質の異なる候補化合物を迅速に提供することが重要であり、抗菌ペプチドポリミキシンを用いて抗菌スペクトルを迅速に改変できた事実は、予測の難しい感染症に対して本研究で確立した手法が機能することを示している。