Inhibition of beta-N-acetylglucosaminidase by glycon-related analogues of the substrate.

Journal article

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.

Authors: Horsch, M; Hoesch, L; Fleet, G; Rast, D

• Publication status: Published
• Journal: Journal of enzyme inhibition
• Volume: 7
• Issue: 1
• Pages: 47-55
• Publication date: 1993-01-01
• DOI: 10.3109/14756369309020188
• ISSN: 8755-5093
• Language: English
• Keywords: Acetylglucosaminidase; Substrate Specificity; Cattle; Animals; Catalysis; Acetylglucosamine; Kidney