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As part of continued efforts to understand the mechanisms of 1,5-α-l-arabinanases better, some arabinan-like iminosugar oligosaccharides were synthesized. An iminosugar analogue of arabinobiose was found to be a good inhibitor of the arabinanase Arb93A from Fusarium graminearum. Structures were determined for complexes of this inhibitor with wild-type Arb93A and a catalytically inactive mutant. [ABSTRACT FROM AUTHOR]

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.

A cellobio-derived isofagomine glycosidase inhibitor (Ki approximately 400 nM) displays an unusual distorted 2,5B (boat) conformation upon binding to cellobiohydrolase Cel6A from Humicola insolens, highlighting the different conformational itineraries used by various glycosidases, with consequences for the design of therapeutic agents.