title: 5-Oxoprolinal: transition-state aldehyde inhibitor of pyroglutamyl-peptide hydrolase.
abstract: Pyroglutamyl-peptide hydrolase (EC 3.4.11.8) removes the N-terminal pyroglutamyl residue from pyroglutamyl-containing peptides such as thyrotropin-releasing hormone (TRH), luteinizing hormone-releasing hormone (LH-RH), neurotensin, and bombesin. The aldehyde analogue of pyroglutamate, 5-oxoprolinal, was synthesized as an active site directed transition-state inhibitor of the enzyme. 5-Oxoprolinal was found to be a potent (Ki = 26 nM) and specific competitive inhibitor of pyroglutamyl-peptide hydrolase. Other aldehydes tested inhibited the enzyme only weakly or not at all. 5-Oxoprolinal blocked the degradation of LH-RH by purified pyroglutamyl-peptide hydrolase. The inhibitor, when injected into mice, inhibited the enzyme after 10 and 30 min. 5-Oxoprolinal should be of value in studies probing the biological significance of pyroglutamyl-peptide hydrolase.
authors.forename: T C
authors.initials: TC
authors.lastname: Friedman
authors.forename: T B
authors.initials: TB
authors.lastname: Kline
authors.forename: S
authors.initials: S
authors.lastname: Wilk
mesh_terms: D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D011751:Pyroglutamyl-Peptidase I / Q000037:antagonists & inhibitors*; D013055:Spectrophotometry, Infrared; D014018:Tissue Distribution
chemical_list: D007202:Indicators and Reagents; C047035:5-oxoprolinal; D011392:Proline; D000626:Aminopeptidases; D011751:Pyroglutamyl-Peptidase I