Discovery of carboxypeptidase Y as a catalyst for the incorporation of sterically demanding α-fluoroalkyl amino acids into peptides

The first example of a direct enzymatic coupling of two different, sterically demanding Cα-fluoroalkyl amino acids to amino acid nucleophiles is reported. N-Protected Ala methyl ester derivatives bearing a methyl-, difluoromethyl-, or trifluoromethyl group, respectively, instead of the α-proton were accepted as substrates by carboxypeptidase Y and could, therefore, be coupled directly to various nucleophiles.