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

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.

• Authors: Michael Schalli, Christina Tysoe, Roland Fischer, Bettina M Pabst, Martin Thonhofer, Eduard Paschke, Tanja Rappitsch, Arnold E Stütz, Marion Tschernutter, Werner Windischhofer, Stephen G Withers
• Journal: Carbohydrate research (Carbohydr Res) Vol. 443-444 Pg. 15-22 (Apr 18 2017) ISSN: 1873-426X [Electronic] Netherlands
• PMID: 28319682 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

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

Topics

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