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Fluorous Iminoalditols: A New Family of Glycosidase Inhibitors and Pharmacological Chaperones
Author(s) -
Schitter Georg,
Steiner Andreas J.,
Pototschnig Gerit,
Scheucher Elisabeth,
Thonhofer Martin,
Tarling Chris A.,
Withers Stephen G.,
Fantur Katrin,
Paschke Eduard,
Mahuran Don J.,
Rigat Brigitte A.,
Tropak Michael B.,
Illaszewicz Carina,
Saf Robert,
Stütz Arnold E.,
Wrodnigg Tanja M.
Publication year - 2010
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.201000192
Subject(s) - moiety , glycoside hydrolase , chemistry , biochemistry , combinatorial chemistry , enzyme , ring (chemistry) , computational biology , stereochemistry , biology , organic chemistry
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.