Inhibition of beta-N-acetylglucosaminidase by glycon-related analogues of the substrate.
Inhibition studies on beta-N-acetylglucosaminidase (EC 3.2.1.30) of widely differing origins (animal, plant, fungus) were carried out with N-acetylglucosaminono-1,5-lactone (1), N-acetylglucosaminono-1,5-lactam (2), 1,5-imino-N-acetylglucosaminitol (3), and N-acetylglucosaminono-1,5-lactone oxime (4). The inhibition was competitive in all cases, and Ki values were generally in the range of 0.15-2 microM, except for the fungal enzyme (5-20 microM). To assess the kinetics of enzyme-inhibitor complex formation, continuous enzyme activity monitoring was done with 3,4-dinitrophenyl-beta-N-acetylglucosaminide as the substrate. A slow approach to the binding-equilibrium in the time scale of minutes could not be observed with any of the inhibitors tested (1-4). The results are evaluated as to the bearing of the enzyme source on best performance of the test compounds, the sub-type of inhibition mechanism is discussed, and suggestions are made for further analogue syntheses as well as potential applications of 1-4 (particularly the O-phenylcarbamoyl derivative of the latter) in biological and medical research.
Horsch
M
M
Department of Plant Biology, University of Zürich, Switzerland.
Hoesch
L
L
Fleet
G W
GW
Rast
D M
DM
D000117:Acetylglucosamine / Q000031:analogs & derivatives / Q000378:metabolism*; D000118:Acetylglucosaminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D002384:Catalysis; D002417:Cattle; D007668:Kidney / Q000201:enzymology; D013379:Substrate Specificity
D000118:Acetylglucosaminidase; D000117:Acetylglucosamine