Evaluation of some substrates and potential inhibitors of tissue pyroglutamyl aminopeptidase I.
A fluorometric enzyme assay was developed to evaluate the ability of a variety of compounds to bind to and/or inhibit pyroglutamyl aminopeptidase I. Among these compounds were a series of chloromethyl ketone analogues of thyrotropin releasing hormone (TRH) which had previously been shown to possess TRH-like activity in the central nervous system and have now been found to be good inhibitors of pyroglutamyl aminopeptidase. Thus, it is suggested that the observed TRH-like CNS activity could derive indirectly from inhibition of endogenous TRH degradation by pyroglutamyl aminopeptidase I.
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois, Chicago 60680.
K S
KS
Svoboda
B L
BL
Currie
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D005456:Fluorescent Dyes; D008099:Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D011751:Pyroglutamyl-Peptidase I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D005456:Fluorescent Dyes; D013973:Thyrotropin-Releasing Hormone; D011751:Pyroglutamyl-Peptidase I