Investigation of original multivalent iminosugars as pharmacological chaperones for the treatment of Gaucher disease

Carbohydr Res. 2016 Jun 24:429:98-104. doi: 10.1016/j.carres.2016.03.007. Epub 2016 Mar 16.

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.

MeSH terms

  • Click Chemistry
  • Enzyme Activation / drug effects
  • Enzyme Reactivators / chemical synthesis*
  • Enzyme Reactivators / pharmacology
  • Fibroblasts / drug effects*
  • Fibroblasts / enzymology
  • Fibroblasts / pathology
  • Gaucher Disease / drug therapy
  • Gaucher Disease / enzymology
  • Gaucher Disease / pathology
  • Glucosylceramidase / chemistry*
  • Glucosylceramidase / deficiency
  • Humans
  • Imino Sugars / chemical synthesis*
  • Imino Sugars / pharmacology
  • Kinetics
  • Lysosomes / drug effects*
  • Lysosomes / enzymology
  • Molecular Targeted Therapy
  • Morpholines / chemistry
  • Prodrugs / chemical synthesis*
  • Prodrugs / pharmacology
  • Protein Binding
  • Protein Folding

Substances

  • Enzyme Reactivators
  • Imino Sugars
  • Morpholines
  • Prodrugs
  • Glucosylceramidase