Optical Control of Antibody Activity by Using Photocleavable Bivalent Peptide–DNA Locks

Antibody‐based molecular recognition plays a central role in today's life sciences, ranging from immunoassays to molecular imaging and antibody‐based therapeutics. Control over antibody activity by using external triggers such as light could further increase the specificity of antibody‐based targeting. Here we present bivalent peptide–DNA ligands containing photocleavable linkers as a noncovalent approach by which to allow photoactivation of antibody activity. Light‐triggered cleavage of the 3‐amino‐3‐(2‐nitrophenyl)propionic acid peptide linker converted the high‐affinity bivalent peptide–DNA lock into weakly binding monovalent ligands, effectively restoring antibody targeting of cell‐surface receptors. In this work, a proof of principle was provided with an anti‐hemagglutinin antibody, but the molecular design of the lock is generic and applicable to any monoclonal antibody for which an epitope or mimotope of sufficient affinity is available.