Targeted protein editing with an antibody-based system

Abstract The chemical modification of proteins is one of the major mechanisms used to regulate the trafficking and function of these macromolecules in the cell. It is therefore of great interest to develop tools to exploit this type of modifications for applications in molecular biology, medicine and biotechnology. Here we present a method of using antibodies to perform post-translational covalent modifications of endogenous proteins in complex environments by exploiting proximity-driven chemistry. The method is based on the ability of antibodies to hold a weakly reactive group adjacently to its intended site of reaction by binding the target protein on a nearby epitope. We illustrate this approach by targeting the green fluorescent protein in increasingly complex environments.