N-Substituted 5-amino-1-hydroxymethyl-cyclopentanetriols: A new family of activity promotors for a GM1-gangliosidosis related human lysosomal β-galactosidase mutant

Carbohydr Res. 2017 Apr 18:443-444:15-22. doi: 10.1016/j.carres.2017.03.009. Epub 2017 Mar 11.

Abstract

From 1,2;3,4-di-O-isopropylidene-α-D-galactopyranose, a series of highly functionalized (hydroxymethyl)cyclopentanes was easily available. In line with reports by Reymond and Jäger on similar structures, these amine containing basic carbasugars are potent inhibitors of β-D-galactosidases and, for the first time, could be shown to act as pharmacological chaperones for GM1-gangliosidosis-associated lysosomal acid β-galactosidase mutant R201C, thus representing a new structural type of pharmacological chaperones for this lysosomal storage disease.

Keywords: Aminocyclopentane; Carbafuranose; G(M1)-Gangliosidosis; Galactosidase inhibitor; Pharmacological chaperone.

MeSH terms

  • Cyclopentanes / chemical synthesis
  • Cyclopentanes / chemistry*
  • Cyclopentanes / pharmacology*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Gangliosidosis, GM1 / enzymology
  • Gangliosidosis, GM1 / genetics*
  • Humans
  • Models, Molecular
  • Molecular Conformation
  • Mutation*
  • beta-Galactosidase / antagonists & inhibitors*
  • beta-Galactosidase / genetics

Substances

  • Cyclopentanes
  • Enzyme Inhibitors
  • acid beta-galactosidase
  • beta-Galactosidase