• Media type: E-Article
  • Title: N‐Acetylgucosaminono‐1,5‐lactone oxime and the corresponding (phenylcarbamoyl)oxime : Novel and potent inhibitors of β‐N‐acetylglucosaminidase : Novel and potent inhibitors of β‐<i>N</i>‐acetylglucosaminidase
  • Contributor: HORSCH, Markus; HOESCH, Lienhard; VASELLA, Andrea; RAST, Dora M.
  • Published: Wiley, 1991
  • Published in: European Journal of Biochemistry
  • Extent: 815-818
  • Language: English
  • DOI: 10.1111/j.1432-1033.1991.tb15976.x
  • ISSN: 0014-2956; 1432-1033
  • Keywords: Biochemistry
  • Abstract: <jats:p>Using <jats:italic>N</jats:italic>‐acetylglucosaminono‐1,5‐lactone (<jats:bold>1</jats:bold>) as the reference, the inhibitory activity of its (formal) derivatives <jats:italic>N</jats:italic>‐acetylglucosaminono‐1,5‐lactone oxime (<jats:bold>2</jats:bold>) and <jats:italic>N</jats:italic>‐acetylglucosaminono‐1,5‐lactone <jats:italic>O</jats:italic>‐(phenylcarbamoyl)‐oxime (<jats:bold>3</jats:bold>) was tested against β‐<jats:italic>N</jats:italic>‐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 <jats:bold>2</jats:bold> was about equally potent as the parent lactone <jats:bold>1</jats:bold>, and 50–400 times more efficient than two recently described new β‐<jats:italic>N</jats:italic>‐acetylglucosaminidase inhibitors. The (phenylcarbamoyl)oxime <jats:bold>3</jats:bold> performed even better, particularly with the fungal enzyme (<jats:italic>K</jats:italic><jats:sub>i</jats:sub>= 40 nM), i.e. was about 350 times more potent than the lactone. In all cases competitive inhibition was observed with 4‐nitrophenyl‐β‐<jats:italic>N</jats:italic>‐acetylglucosaminide as the substrate. With <jats:italic>K</jats:italic><jats:sub>i</jats:sub>/<jats:italic>K</jats:italic><jats:sub>m</jats:sub> ratios up to 3300 for <jats:bold>2</jats:bold> and 13600 for <jats:bold>3</jats:bold>, 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.</jats:p>
  • Description: <jats:p>Using <jats:italic>N</jats:italic>‐acetylglucosaminono‐1,5‐lactone (<jats:bold>1</jats:bold>) as the reference, the inhibitory activity of its (formal) derivatives <jats:italic>N</jats:italic>‐acetylglucosaminono‐1,5‐lactone oxime (<jats:bold>2</jats:bold>) and <jats:italic>N</jats:italic>‐acetylglucosaminono‐1,5‐lactone <jats:italic>O</jats:italic>‐(phenylcarbamoyl)‐oxime (<jats:bold>3</jats:bold>) was tested against β‐<jats:italic>N</jats:italic>‐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 <jats:bold>2</jats:bold> was about equally potent as the parent lactone <jats:bold>1</jats:bold>, and 50–400 times more efficient than two recently described new β‐<jats:italic>N</jats:italic>‐acetylglucosaminidase inhibitors. The (phenylcarbamoyl)oxime <jats:bold>3</jats:bold> performed even better, particularly with the fungal enzyme (<jats:italic>K</jats:italic><jats:sub>i</jats:sub>= 40 nM), i.e. was about 350 times more potent than the lactone. In all cases competitive inhibition was observed with 4‐nitrophenyl‐β‐<jats:italic>N</jats:italic>‐acetylglucosaminide as the substrate. With <jats:italic>K</jats:italic><jats:sub>i</jats:sub>/<jats:italic>K</jats:italic><jats:sub>m</jats:sub> ratios up to 3300 for <jats:bold>2</jats:bold> and 13600 for <jats:bold>3</jats:bold>, 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.</jats:p>
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  • Access State: Open Access