Tyrosinase-Mediated Oxidative Coupling of Tyrosine Tags on Peptides and Proteins

We report a strategy for chemical protein modification by using tyrosinase enzymes to oxidize exposed tyrosine residues on protein N or C-termini. We explore the chemical space for coupling partners in this reaction and find combinations that can proceed in near quantitative conversion. This strategy is used to conjugate a dye onto a Trastuzumab antibody fragment and a Protein L fragment and demonstrate that these constructs can be used as immunostaining reagents.