Development of fragment antibody targeting system based on antigen-templated chemical reaction

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06453
• 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: Kyoto University
• Principal Investigator: Akiba Hiroki 京都大学, 薬学研究科, 助教 (70739945)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 抗体 / コンジュゲート化学 / テンプレート反応

Outline of Final Research Achievements

In this study, we developed biepitopic antigen-templated chemical reaction (BATER) as a novel kind of templated chemistry. Two antibody fragments binding two different epitopes of the antigen are conjugated with a pair of chemical groups that react and form covalent bonds between them. On binding of two antibody fragments to the antigen, two reacting groups are in proximity and the covalent bond formation occurs. Through this process, monovalent antibody fragments are turned into bivalent molecule with strong interaction. The reaction was proven by fluorogenic click chemistry.

Free Research Field

蛋白質工学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果として新たに開発された抗原テンプレート反応は、当初目的とした低分子化抗体ターゲティングシステムの基盤技術としてさらなる開発を進めることで、従来抗体とは異なる特性を示す抗原結合モダリティの実用化につながる。このほかにも抗原分子上に結合した抗体表面での化学反応というシステムを、薬剤送達や抗原検出など多様な応用につなげることで、抗体が従来、医薬や生物科学に利用されてきた領域をさらに広げることができる。