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

doi:10.1039/b709681j

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

by Adrian Scaffidi, Keith A Stubbs, Rebecca J Dennis, Edward J Taylor, Gideon J Davies, David J Vocadlo, Robert V Stick

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Organic and Biomolecular Chemistry (2007)

Volume: 5, Issue: 18, Pages: 3013-3019

DOI: 10.1039/b709681j
PubMed: 17728868

Available from Organic and Biomolecular Chemistry

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Abstract

The synthesis of an analogue of 6-epi-valienamine bearing an acetamido group and its characterisation as an inhibitor of beta-N-acetylglucosaminidases are described. The compound is a good inhibitor of both human O-GlcNAcase and human beta-hexosaminidase, as well as two bacterial beta-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.