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 beta-elimination of phosphate from the phosphopeptide Arg-Ala-Ser(P)-Val-Ala. The dehydroalanine-containing peptide formed was a competitive inhibitor with a K-i of 0.02 +/- 0.01 mu M. This study demonstrated that replacing a serine residue in a good inhibitor with a dehydroalanine residue reduced the K-i 45 times. It is proposed that dehydroalanine-containing peptides could be of interest in the development of inhibitors for other peptidases as well. (C) 1994 Academic Press, Inc.