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

Area of Science:

• Chemical Biology
• Immunology
• Bioconjugation Chemistry

Background:

• Proximity-induced reactions offer site-specificity and speed via template interactions.
• Antibody-antigen interactions have not been previously utilized to induce chemical reactions.
• Novel templating strategies are needed for controlled chemical transformations.

Purpose of the Study:

• To introduce a novel biepitopic antigen-templated chemical reaction (BATER) system.
• To demonstrate the acceleration of chemical reactions using antibody-antigen recognition.
• To establish a method for visualizing and optimizing BATER for biological applications.

Main Methods:

• Conjugating reactive functional groups to two antibodies targeting distinct epitopes of the same antigen.
• Utilizing fluorogenic click chemistry to monitor and optimize the BATER process.
• Investigating the influence of linker length and antibody epitope selection on reaction kinetics.

Main Results:

• BATER accelerates chemical reactions in the presence of a specific antigen.
• Reaction rates are dependent on the length of the linkers connecting antibodies.
• The selection of antibody epitopes significantly impacts the reaction speed.
• Fluorogenic click chemistry effectively visualizes BATER progress for optimization.

Conclusions:

• Biepitopic antigen-templated chemical reaction (BATER) is a viable strategy for proximity-induced reactions.
• Antibody-antigen interactions can be harnessed to template and accelerate chemical transformations.
• The BATER system demonstrates potential for diverse applications within living systems.