A new type of pharmacological chaperone for G M1-gangliosidosis related human lysosomal β-galactosidase: N-Substituted 5-amino-1-hydroxymethyl-cyclopentanetriols

Bioorg Med Chem Lett. 2017 Aug 1;27(15):3431-3435. doi: 10.1016/j.bmcl.2017.05.086. Epub 2017 May 30.

Abstract

N-Functionalized amino(hydroxymethyl)cyclopentanetriols 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 thus representing a new structural type of pharmacological chaperones for this lysosomal storage disease.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amination
  • Animals
  • Cattle
  • Cyclopentanes / chemistry*
  • Cyclopentanes / pharmacology*
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Gangliosidosis, GM1 / drug therapy*
  • Gangliosidosis, GM1 / enzymology
  • Humans
  • Lysosomes / drug effects
  • Lysosomes / enzymology
  • Methylation
  • beta-Galactosidase / antagonists & inhibitors*
  • beta-Galactosidase / metabolism

Substances

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