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Design and Synthesis of Highly Potent and Selective Pharmacological Chaperones for the Treatment of Gaucher's disease
Author(s) -
Compain Philippe,
Martin Olivier R.,
Boucheron Charlotte,
Godin Guillaume,
Yu Liang,
Ikeda Kyoko,
Asano Naoki
Publication year - 2006
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200600217
Subject(s) - potency , pharmacology , xylitol , iminosugar , chemistry , hydroxymethyl , glucocerebrosidase , biochemistry , enzyme , medicine , stereochemistry , in vitro , fermentation
Remove to improve . Removal of the hydroxymethyl groups in 1 to give 2 significantly enhances inhibitory potency towards glucosylceramide β‐glucosidase (GCase) and abolishes inhibition towards α‐glucosidases. Xylitol 2 doubles the residual activity of GCase in fibroblasts from Gaucher patients at subinhibitory concentration (10 n M ). This compound is therefore a promising candidate for the development of small‐molecule drugs for the treatment of Gaucher's disease without the side effects associated with α‐glucosidase inhibition.