Inhibition of recombinant dipeptidyl peptidase III by synthetic hemorphin-like peptides

In order to find the most effective antagonist for dipeptidyl peptidase III degrading enkephalin, we synthesized hemorphin-like pentapeptides with aliphatic or aromatic amino acids at the N-termini, such as VVYPW, LVYPW, IVYPW, YVYPW, FVYPW and WVYPW. Among those pentapeptides, IVYPW and WVYPW showed the strongest inhibitory activity toward rDPP III. The K-i values of IVYPW and WVYPW were 0.100+/-0.011 and 0.126+/-0.015 muM (mean+/-S.E.), respectively. The order of Ki values was Ile greater than or equal to Trp > Phe greater than or equal to Tyr > Leu > Ala > Val > Ser > Gly. rDPP III activity is inhibited in a non-competitive manner by these peptides. The peptide VYPW did not inhibit rDPP III activity, but the sequence is essential for the expression of inhibitory activity. (C) 2003 Elsevier Inc. All rights reserved.