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Fluorous Iminoalditols: A New Family of Glycosidase Inhibitors and Pharmacological Chaperones

TitleFluorous Iminoalditols: A New Family of Glycosidase Inhibitors and Pharmacological Chaperones
Publication TypeJournal Article
Year of Publication2010
AuthorsSchitter, G, Steiner, AJ, Pototschnig, G, Scheucher, E, Thonhofer, M, Tarling, CA, Withers, SG, Fantur, K, Paschke, E, Mahuran, DJ, Rigat, BA, Tropak, MB, Illaszewicz, C, Saf, R, Stuetz, AE, Wrodnigg, TM
JournalCHEMBIOCHEM
Volume11
Pagination2026-2033
Date PublishedSEP 24
ISSN1439-4227
Abstract

A collection of new reversible glycosidase inhibitors of the iminoalditol type featuring N-substituents containing perfluorinated regions has been prepared for evaluation of physicochemical, biochemical and diagnostic properties. The vast variety of feasible oligofluoro moieties allows for modular approaches to customised structures according to the intended applications, which are influenced by the fluorine content as well as the distance of the fluorous moiety from the ring nitrogen. The first examples, in particular in the D-galacto series, exhibited excellent inhibitory activities. A preliminary screen with two human cell lines showed that, at subinhibitory concentrations, they are powerful pharmacological chaperones enhancing the activities of the catalytically handicapped lysosomal D-galactosidase mutants associated with GM1 gangliosidosis and Morquio B disease.

DOI10.1002/cbic.201000192