Abstract
The selective amino acid chemical modifications selectively modify only one of 20 canonical amino acids in peptides and proteins. Lysine and cysteine are often targeted for selective modifications using the nucleophilicity of their side chains. These reactions are applied to antibody-drug conjugates for clinical use. Recently, selective modifications targeting residues other than lysine and cysteine have been reported. However, small peptides and proteins have been the main substrates. Conjugation and functionalization of antibodies, large protein complexes comprising several domains and subunits, are still limited. In this manuscript, we discuss selective tyrosine, tryptophan, and methionine modifications based on the unique redox properties of these amino acids and reactants, their applications to antibody modifications, and the functional evaluation of the conjugates.
