Challenges to create natural product-drug conjugate starting from screening of natural products that bind to membrane proteins

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19115
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 37:Biomolecular chemistry and related fields
• Research Institution: Kyushu University
• Principal Investigator: Matsumori Nobuaki 九州大学, 理学研究院, 教授 (50314357)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: 膜タンパク質 / 脂質 / 天然物 / 相互作用 / 金ナノ粒子

Outline of Final Research Achievements

This research aims to create “natural product-drug conjugate", starting from our original technology. We have established a technique for stably immobilizing membrane proteins on the surface of gold nanoparticles coated with a thin lipid film. Furthermore, by utilizing this technique, we have developed an experimental scheme to recover membrane protein-binding natural products from a mixture of natural lipids and natural organic compounds, and to detect them by LC-MS. This method made it possible to efficiently obtain natural products with high affinity for membrane proteins.
At the same time, a new method for detection of natural products with high affinity for membrane proteins using the strong red color of gold nanoparticles was also developed. By applying this method to compound libraries immobilized on micro-arrays, the screening of natural products having high affinity to membrane proteins can be made more efficient.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

化合物ライブラリーを利用した創薬研究は、目的とする生理活性を有する化合物をいかに探索するかに主眼が置かれてきた。本研究では生理活性を指標とせず、標的膜タンパク質との強い親和性を有する天然物を探索する。ここで代表者の開発した膜タンパク質親和性天然物探索法を活用する。このようにして得られた天然物を起点として、その親和性を保ちつつ、抗体－薬物複合体のように低分子薬剤を結合させる。これにより、高い標的特異性と薬理活性を併せ持つ画期的な新薬を開発する創薬戦略が実現する。本研究ではこの「天然物－薬物複合体」医薬創成の目途を立てることができ、新たな創薬分野開拓への重要な端緒となった。