Targeted ProteinModification with an Antibody-BasedSystem

Abstract

The chemical modification of proteins is one of the majormechanismsused to regulate the properties and functions of these macromoleculesin the cell. It is therefore of great interest to develop tools toexploit this type of modification for applications in molecular biology,medicine, and biotechnology. Here we present a method of using antibodiesto perform post-translational covalent modifications of endogenousproteins in complex environments by exploiting proximity-driven chemistry.The method is based on the ability of antibodies to hold a weaklyreactive group close to its intended site of reaction by binding thetarget protein on a nearby epitope. We characterize this approachby modifying the green fluorescent protein in increasingly complexenvironments and illustrate its applicability by targeting the disease-associatedprotein beta-2 microglobulin.