Design and synthesis of highly potent and selective pharmacological chaperones for the treatment of Gaucher's disease

被引：151

作者：

Compain, Philippe

Martin, Olivier R.

Boucheron, Charlotte

Godin, Guillaume

Yu, Liang

Ikeda, Kyoko

Asano, Naoki

机构：

[1] Univ Orleans, ICOA, UMR 6005 CNRS, F-45067 Orleans, France

[2] Hokuriku Univ, Fac Pharmaceut Sci, Kanazawa, Ishikawa 9201181, Japan

来源：

CHEMBIOCHEM | 2006年 / 7卷 / 09期

关键词：

chemical chaperones; drug design; enzymes; Gaucher's disease; iminosugar; inhibitors;

D O I：

10.1002/cbic.200600217

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 sub-inhibitory concentration (10 nM). 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. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.

引用

页码：1356 / 1359

页数：4

共 30 条

[21] Membrane disruption and cytotoxicity of hydrophobic N-alkylated imino sugars is independent of the inhibition of protein and lipid glycosylation [J].