On the degradation of dermorphin and D-Arg2-dermorphin analogs by a soluble rat brain extract.
Degradation of dermorphin, [D-Arg2]dermorphin and [D-Arg2, Gly3, Phe4]dermorphin in a soluble rat brain extract was examined. The former two heptapeptides were degraded in a similar fashion to produce corresponding N-terminal tetrapeptide as the main degradation product along with the parallel release of Tyr5, Pro6 and Ser7-NH2. Tyr-D-Arg-Phe-Gly showed a good enzymatic stability. When captopril, an angiotensin-converting enzyme inhibitor, was present in the incubation mixture, hydrolysis of the Gly4-Tyr5 bond was markedly suppressed and resulted in release of the corresponding N-terminal hexapeptide as the main degradation product. Combined use of captopril and amastatin, an aminopeptidase inhibitor, markedly suppressed the hydrolysis of these peptides. On the other hand, [D-Arg2, Gly3, Phe4]dermorphin was hydrolyzed easier than the other two heptapeptides and considerable amounts of Tyr1 and Phe4 were released after 20 hr incubation while the N-terminal tetrapeptide, Tyr-D-Arg-Gly-Phe, showed a good enzymatic stability. On the basis of these results, possible degradation pathways of these heptapeptides were discussed.
Sasaki
Y
Y
Hosono
M
M
Matsui
M
M
Fujita
H
H
Suzuki
K
K
Sakurada
S
S
Sakurada
T
T
Kisara
K
K
D000596:Amino Acids / Q000032:analysis; D000701:Analgesics, Opioid / Q000138:chemical synthesis / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D002216:Captopril / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000378:metabolism; D007700:Kinetics; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D018847:Opioid Peptides; D010455:Peptides; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000596:Amino Acids; D000701:Analgesics, Opioid; D000900:Anti-Bacterial Agents; D009842:Oligopeptides; D018847:Opioid Peptides; D010455:Peptides; C030058:dermorphin; C016977:amastatin; C045484:dermorphin, Arg(2)-; C046268:dermorphin, Arg(2)-Gly(3)-Phe(4)-; D002216:Captopril