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

Open Access
Publisher Website
Google Scholar
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 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 (Ki= 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 Ki/Km 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.