A Proximity-Induced Fluorogenic Reaction Triggered by Antibody-Antigen Interactions with Adjacent Epitopes

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.

Automated summary

Proximity-induced chemical reactions are rapid and site-specific, taking advantage of high affinity and highly selective interactions with templates. A biepitopic antigen-templated chemical reaction (BATER) is proposed, where reactive functional groups are conjugated to two antibodies that interact with two epitopes of the same antigen to accelerate the reaction. Visualizing the progress of BATER using fluorogenic click chemistry allows for optimal antibody selection and linker design.