A 1-acetamido derivative of 6-epi-valienamine: an inhibitor of a diverse group of β-N-acetylglucosaminidases

Scaffidi, Adrian and Stubbs, Keith A. and Dennis, Rebecca J. and Taylor, Edward J. and Davies, Gideon J. and Vocadlo, David J. and Stick, Robert V. (2007) A 1-acetamido derivative of 6-epi-valienamine: an inhibitor of a diverse group of β-N-acetylglucosaminidases. Organic & Biomolecular Chemistry, 5 (18). pp. 3013-3019. ISSN 1477-0520

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Full text URL: http://dx.doi.org/10.1039/B709681J

Abstract

The synthesis of an analogue of 6-epi-valienamine bearing an acetamido group and its characterisation as an inhibitor of β-N-acetylglucosaminidases are described. The compound is a good inhibitor of both human O-GlcNAcase and human β-hexosaminidase, as well as two bacterial β-N-acetylglucosaminidases. A 3-D structure of the complex of Bacteroides thetaiotaomicron BtGH84 with the inhibitor shows the unsaturated ring is surprisingly distorted away from its favoured solution phase conformation and reveals potential for improved inhibitor potency.

Item Type:Article
Additional Information:The synthesis of an analogue of 6-epi-valienamine bearing an acetamido group and its characterisation as an inhibitor of β-N-acetylglucosaminidases are described. The compound is a good inhibitor of both human O-GlcNAcase and human β-hexosaminidase, as well as two bacterial β-N-acetylglucosaminidases. A 3-D structure of the complex of Bacteroides thetaiotaomicron BtGH84 with the inhibitor shows the unsaturated ring is surprisingly distorted away from its favoured solution phase conformation and reveals potential for improved inhibitor potency.
Keywords:β-N-acetylglucosaminidases, 6-epi-valienamine
Subjects:C Biological Sciences > C700 Molecular Biology, Biophysics and Biochemistry
Divisions:College of Science > School of Life Sciences
ID Code:6158
Deposited By: Edward Taylor
Deposited On:18 Sep 2012 15:31
Last Modified:13 Mar 2013 09:13

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