Abstract
N-(10-Chloro-9-anthracenemethyl)isofagomine 5 and N-(10-chloro-9-anthracenemethyl)-1-deoxynojirimycin 6 were prepared, and their inhibition of almond β-glucosidase was measured. The isofagomine derivative 5 was found to be a potent inhibitor, while the 1-deoxynojirimycin derivative 6 displayed no inhibition at the concentrations investigated. Fluorescence spectroscopy of 5 with almond β-glucosidase at different pH values showed that the inhibitor nitrogen is not protonated when bound to the enzyme. Analysis of pH inhibition data confirmed that 5 binds as the amine to the enzyme's unprotonated dicarboxylate form. This is a radically different binding mode than has been observed with isofagomine and other iminosugars in the literature.
MeSH terms
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Chemistry Techniques, Synthetic
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / metabolism
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Enzyme Inhibitors / pharmacology*
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Glucosamine / analogs & derivatives
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Glucosamine / chemical synthesis
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Glucosamine / chemistry
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Glucosamine / metabolism
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Glucosamine / pharmacology
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Hydrogen-Ion Concentration
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Imino Pyranoses / chemical synthesis
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Imino Pyranoses / chemistry*
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Imino Pyranoses / metabolism
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Imino Pyranoses / pharmacology
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Kinetics
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Protons
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Prunus dulcis / enzymology
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Spectrometry, Fluorescence
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Structure-Activity Relationship
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beta-Glucosidase / antagonists & inhibitors*
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beta-Glucosidase / metabolism
Substances
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1-deoxy-nojirimycin
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Enzyme Inhibitors
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Imino Pyranoses
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N-(10-chloro-9-anthracenemethyl)1-deoxynojirimycin
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N-(10-chloro-9-anthracenemethyl)isofagomine
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Protons
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isofagomine
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beta-Glucosidase
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Glucosamine