Abstract
Multivalent iminosugars conjugated with a morpholine moiety and/or designed as prodrugs have been prepared and evaluated as new classes of pharmacological chaperones for the treatment of Gaucher disease. This study further confirms the interest of the prodrug concept and shows that the addition of a lysosome-targeting morpholine unit into iminosugar cluster structures has no significant impact on the chaperone activity on Gaucher cells.
Keywords:
Click-chemistry; Gaucher disease; Iminosugars; Lysosomal diseases; Multivalency; Pharmacological chaperones.
Copyright © 2016 Elsevier Ltd. All rights reserved.
MeSH terms
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Click Chemistry
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Enzyme Activation / drug effects
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Enzyme Reactivators / chemical synthesis*
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Enzyme Reactivators / pharmacology
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Fibroblasts / drug effects*
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Fibroblasts / enzymology
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Fibroblasts / pathology
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Gaucher Disease / drug therapy
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Gaucher Disease / enzymology
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Gaucher Disease / pathology
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Glucosylceramidase / chemistry*
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Glucosylceramidase / deficiency
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Humans
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Imino Sugars / chemical synthesis*
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Imino Sugars / pharmacology
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Kinetics
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Lysosomes / drug effects*
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Lysosomes / enzymology
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Molecular Targeted Therapy
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Morpholines / chemistry
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Prodrugs / chemical synthesis*
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Prodrugs / pharmacology
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Protein Binding
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Protein Folding
Substances
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Enzyme Reactivators
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Imino Sugars
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Morpholines
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Prodrugs
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Glucosylceramidase