DNA‐Catalyzed Introduction of Azide at Tyrosine for Peptide Modification

We show that DNA enzymes (deoxyribozymes) can introduce azide functional groups at tyrosine residues in peptide substrates. Using in vitro selection, we identified deoxyribozymes that transfer the 2′‐azido‐2′‐deoxyadenosine 5′‐monophosphoryl group (2′‐Az‐dAMP) from the analogous 5′‐triphosphate (2′‐Az‐dATP) onto the tyrosine hydroxyl group of a peptide, which is either tethered to a DNA anchor or free. Some of the new deoxyribozymes are general with regard to the amino acid residues surrounding the tyrosine, while other DNA enzymes are sequence‐selective. We use one of the new deoxyribozymes to modify free peptide substrates by attaching PEG moieties and fluorescent labels.