Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, 606-8501, Japan.
National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki City, Osaka, 567-0085, Japan.
Angew Chem Int Ed Engl. 2023 Jul 24;62(30):e202306431. doi: 10.1002/anie.202306431. Epub 2023 Jun 16.
Proximity-induced chemical reactions are site-specific and rapid by taking advantage of their high affinity and highly selective interactions with the template. However, reactions induced solely by antibody-antigen interactions have not been developed. Herein, we propose a biepitopic antigen-templated chemical reaction (BATER) as a novel template reaction. In BATER, reactive functional groups are conjugated to two antibodies that interact with two epitopes of the same antigen to accelerate the reaction. We developed a method for visualizing the progress of BATER using fluorogenic click chemistry for optimal antibody selection and linker design. The reaction is accelerated in the presence of a specific antigen in a linker length-dependent manner. The choice of the antibody epitope is important for a rapid reaction. This design will lead to various applications of BATER in living systems.
近程诱导化学反应具有高亲和力和高度选择性与模板相互作用的特点,因此具有特异性和快速性。然而,仅仅利用抗体-抗原相互作用诱导的反应尚未得到开发。在此,我们提出了一种双表位抗原模板化学反应(BATER)作为一种新型模板反应。在 BATER 中,反应性官能团与两种抗体连接,这两种抗体与同一抗原的两个表位相互作用,从而加速反应。我们开发了一种使用荧光 click 化学来可视化 BATER 进展的方法,以用于最佳的抗体选择和连接子设计。该反应在特定抗原的存在下以连接子长度依赖性的方式加速。抗体表位的选择对于快速反应很重要。这种设计将导致 BATER 在生命系统中的各种应用。