Use of a Dehydroalanine-Containing Peptide as an Efficient Inhibitor of Tripeptidyl Peptidase II

Tripeptidyl peptidase II is an intracellular exopeptidase, which has been purified from rat liver and human erythrocytes. An efficient specific inhibitor was obtained through β-elimination of phosphate from the phosphopeptide Arg-Ala-Ser(P)-Val-Ala. The dehydroalanine-containing peptide formed was a competitive inhibitor with a Ki of 0.02 ± 0.01 μM. This study demonstrated that replacing a serine residue in a good inhibitor with a dehydroalanine residue reduced the Ki 45 times. It is proposed that dehydroalanine-containing peptides could be of interest in the development of inhibitors for other peptidases as well.