Abstract
The highly stereocontrolled de novo synthesis of l-NBDNJ (the unnatural enantiomer of the iminosugar drug Miglustat) and a preliminary evaluation of its chaperoning potential are herein reported. l-NBDNJ is able to enhance lysosomal α-glucosidase levels in Pompe disease fibroblasts, either when administered singularly or when coincubated with the recombinant human α-glucosidase. In addition, differently from its d-enantiomer, l-NBDNJ does not act as a glycosidase inhibitor.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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1-Deoxynojirimycin / analogs & derivatives*
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1-Deoxynojirimycin / chemical synthesis
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1-Deoxynojirimycin / chemistry
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1-Deoxynojirimycin / pharmacology
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Allosteric Regulation / drug effects
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Cell Line
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Enzyme Activation / drug effects*
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Fibroblasts / drug effects*
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Fibroblasts / enzymology
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Fibroblasts / metabolism
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Glycogen Storage Disease Type II / drug therapy*
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Glycogen Storage Disease Type II / enzymology
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Glycogen Storage Disease Type II / metabolism
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Humans
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Lysosomes / drug effects
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Lysosomes / enzymology
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Lysosomes / metabolism
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Models, Molecular
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Stereoisomerism
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alpha-Glucosidases / metabolism*
Substances
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Enzyme Inhibitors
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1-Deoxynojirimycin
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miglustat
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alpha-Glucosidases