title: Bivalent transition-state analogue inhibitors of human glyoxalase I.
abstract: A new class of competitive inhibitors of homodimeric human glyoxalase I has been created by cross-linking two molecules of the transition-state analogue S-(N-4-chlorophenyl-N-hydroxycarbamoyl)glutathione (CHG) through their gamma-glutamyl-NH(2) groups with poly-beta-alanyl tethers of differing length: [CHG(beta-ala)n](2) suberate diamide (n = 1-7). The strongest inhibitors of this antitumor target enzyme likely bind simultaneously to the active site on each subunit to give K(i) values as small as 0.96 nM (n = 6). [structure: see text]
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, Baltimore, MD 21250, USA.
authors.forename: Zhe-Bin
authors.initials: ZB
authors.lastname: Zheng
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Creighton
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D013869:Thiolester Hydrolases / Q000037:antagonists & inhibitors; D000099301:Hydroxyacylglutathione Hydrolase
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D005978:Glutathione; D007791:Lactoylglutathione Lyase; D013869:Thiolester Hydrolases; D000099301:Hydroxyacylglutathione Hydrolase