N ‐Acetylgucosaminono‐1,5‐lactone oxime and the corresponding (phenylcarbamoyl)oxime

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 β‐ N ‐acetylglucosaminidase of different origins (animal, plant, fungus). Displaying inhibition constants of 0.45 μM and 0.62 μM, 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 β‐ N ‐acetylglucosaminidase inhibitors. The (phenylcarbamoyl)oxime 3 performed even better, particularly with the fungal enzyme ( K i = 40 nM), i.e. was about 350 times more potent than the lactone. In all cases competitive inhibition was observed with 4‐nitrophenyl‐β‐ N ‐acetylglucosaminide as the substrate. With K i / K m ratios up to 3300 for 2 and 13600 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.