Abstract
Competitive inhibitors of either α-galactosidase (α-Gal) or β-galactosidase (β-Gal) with high affinity and selectivity have been accessed by exploiting aglycone interactions with conformationally locked sp(2)-iminosugars. Selected compounds were profiled as potent pharmacological chaperones for mutant lysosomal α- and β-Gal associated with Fabry disease and GM(1) gangliosidosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology*
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Fabry Disease / drug therapy*
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Fabry Disease / enzymology
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Fabry Disease / genetics
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Fibroblasts / drug effects
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Fibroblasts / enzymology
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Fibroblasts / metabolism
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Gangliosidosis, GM1 / drug therapy*
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Gangliosidosis, GM1 / enzymology
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Gangliosidosis, GM1 / genetics
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Humans
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Imino Sugars / chemistry
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Models, Molecular
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Mutation
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alpha-Galactosidase / antagonists & inhibitors*
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alpha-Galactosidase / genetics
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beta-Galactosidase / antagonists & inhibitors*
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beta-Galactosidase / genetics
Substances
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Enzyme Inhibitors
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Imino Sugars
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alpha-Galactosidase
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beta-Galactosidase