title: Synthesis and GGCT Inhibitory Activity of N-Glutaryl-L-alanine Analogues.
abstract: γ-Glutamylcyclotransferase (GGCT) is an important enzyme that cleaves γ-glutamyl-amino acid in the γ-glutamyl cycle to release 5-oxoproline and amino acid. Eighteen N-acyl-L-alanine analogues including eleven new compounds have been synthesized and examined for their inhibitory activity against recombinant human GGCT protein. Simple N-glutaryl-L-alanine was found to be the most potent inhibitor for GGCT. Other N-glutaryl-L-alanine analogues having methyl and dimethyl substituents at the 2-position were moderately effective, while N-(3R-aminoglutary)-L-alanine, the substrate having an (R)-amino group at the 3-position or N-(N-methyl-3-azaglutaryl)-L-alanine, the substrate having an N-methyl substituent on the 3-azaglutaryl carbon, in constract, exhibited excellent inhibition properties.
authors.affiliation: Department of Clinical Oncology, Kyoto Pharmaceutical University.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ii
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Yoshiki
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Hoshiya
authors.forename: Jun'ichi
authors.initials: J
authors.lastname: Uenishi
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D005722:gamma-Glutamylcyclotransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; C572776:GGCT protein, human; D005722:gamma-Glutamylcyclotransferase; D000409:Alanine