title: N-acetylglucosaminono-1,5-lactone oxime and the corresponding (phenylcarbamoyl)oxime. Novel and potent inhibitors of beta-N-acetylglucosaminidase.
abstract: Using N-acetylglucosaminono-1,5-lactone (1) as the reference, the inhibitory activity of its (formal) derivatives N-acetylglucosaminono-1,5-lactone oxime (2) and N-acetylglucosaminono-1,5-lactone O-(phenylcarbamoyl)-oxime (3) was tested against beta-N-acetylglucosaminidase of different origins (animal, plant, fungus). Displaying inhibition constants of 0.45 microM and 0.62 microM, for the animal and plant enzyme, respectively, the simple oxime 2 was about equally potent as the parent lactone 1, and 50-400 times more efficient than two recently described new beta-N-acetylglucosaminidase inhibitors. The (phenylcarbamoyl)oxime 3 performed even better, particularly with the fungal enzyme (Ki = 40 nM), i.e. was about 350 times more potent than the lactone. In all cases competitive inhibition was observed with 4-nitrophenyl-beta-N-acetylglucosaminide as the substrate. With Ki/Km ratios up to 3300 for 2 and 13,600 for 3, the mode of action of these novel inhibitors is probably that of transition state mimicry. Suggestions are made for their use as a tool in biological research.
authors.affiliation: Institute of Plant Biology, University of Zürich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Horsch
authors.forename: L
authors.initials: L
authors.lastname: Hoesch
authors.forename: A
authors.initials: A
authors.lastname: Vasella
authors.forename: D M
authors.initials: DM
authors.lastname: Rast
mesh_terms: D000117:Acetylglucosamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000118:Acetylglucosaminidase / Q000037:antagonists & inhibitors*; D000818:Animals; D002417:Cattle; D005658:Fungi / Q000201:enzymology; D007700:Kinetics; D007783:Lactones / Q000494:pharmacology*; D010091:Oximes / Q000494:pharmacology*; D048448:Phenylcarbamates
chemical_list: D007783:Lactones; D010091:Oximes; D048448:Phenylcarbamates; C068834:N-acetylglucosaminono-1,5-lactoneoxime; C068836:N-acetylglucosaminono-1,5-lactone O-(phenylcarbamoyl)oxime; D000118:Acetylglucosaminidase; D000117:Acetylglucosamine