Selective Staudinger Modification of Proteins Containing p‐Azidophenylalanine

The unnatural amino acid p-azidophenylalanine was genetically introduced into a phage-displayed peptide and mutant Z-domain protein. These azide-containing proteins were selectively and efficiently modified by using fluorescein-derived phosphines and the Staudinger ligation reaction (see picture). This work provides a powerful new tool for the selective modification of proteins with a variety of synthetic agents.