Chemical modification of polypeptides via metal-mediated reaction

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06482
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
• Research Institution: Keio University
• Principal Investigator: Hanaya Kengo 慶應義塾大学, 薬学部(芝共立), 講師 (50637262)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 化学修飾 / N末端アミノ酸 / タンパク質 / アルドール反応 / 銅イオン

Outline of Final Research Achievements

Bioconjugation reactions that enable the incorporation of artificial molecules, such as drugs, into specific amino acids within proteins have been continuously developed to fulfill the growing demand for applications in both industrial settings and fundamental chemical biology research. This study aimed to develop a method for chemically modifying neighboring amino acids using the N-terminal amino group of the protein. As a result of the research, a new chemical modification method for N-terminal amino acids of proteins utilizing a copper ion-mediated aldol reaction was successfully developed. This method was applicable to the preparation of antibody-drug conjugates.

Free Research Field

有機化学

Academic Significance and Societal Importance of the Research Achievements

現在、タンパク質中のシステインを標的にした化学修飾法が広く利用されている。しかし、この手法は対象のタンパク質がシステインを持たない場合に適用できない。逆に、同一アミノ酸を複数個含む場合、特定の１箇所のみを化学修飾するのは困難である。一方、N末端アミノ酸はタンパク質に必ず１箇所存在する。そのため、本研究で開発したN末端アミノ酸の化学修飾法は、広範なタンパク質の化学修飾に応用できる可能性がある。