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 microM (mean+/-S.E.), respectively. The order of K(i) values was Ile> or =Trp>Phe> or =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.
Chiba
Takehiro
T
Department of Orthopaedics, Nagoya City University Medical School, Mizuho-ku, 467-8601 Nagoya, Japan.
Li
Yao-Hua
YH
Yamane
Takuya
T
Ogikubo
Osamu
O
Fukuoka
Muneyoshi
M
Arai
Ryohachi
R
Takahashi
Sho
S
Ohtsuka
Takanobu
T
Ohkubo
Iwao
I
Matsui
Nobuo
N
D000818:Animals; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D004745:Enkephalins / Q000494:pharmacology; D006454:Hemoglobins / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013116:Spinal Cord / Q000737:chemistry
D004745:Enkephalins; D006454:Hemoglobins; D010455:Peptides; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C100152:dipeptidyl peptidase III