Development and Application of New Chemical Modification of Proteins Based on Spacial Control

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K15957
• 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: Kyushu University
• Principal Investigator: Yoritate Makoto 九州大学, 薬学研究院, 助教 (70843788)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: タンパク質修飾 / 抗体薬物複合体 / C-グリコシド

Outline of Final Research Achievements

Regioselective modification methods of proteins are an important technology in protein engineering, including antibody-drug conjugates (ADCs) and PROTACs, which have attracted much attention in recent years. Due to its high nucleophilicity, cysteine selective protein modification with Michael acceptors is the most reliable method. On the other hand, lysine-selective modification is not easy because lysines on the surface of proteins are more abundant than cysteine. Therefore, we have been working on the development of a new reversible lysine-selective modification using quinone methides as active intermediates. Further optimization of the reactivity will be performed in the future.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

タンパク質の位置選択的修飾法は、近年注目されている抗体薬物複合体（ADC）やPROTACなどを含む、プロテインエンジニアリングにおいて重要な技術である。特に、近年認可されたADC薬であるエンハーツは今後のがん治療を担う医薬品として注目されている。さらに薬効が高く均質なADCを作るためには、抗体-薬物比を高く・均一に保つことが求められる。本研究が完成すれば、医薬品の開発に貢献することが期待される。