title: Fluorous iminoalditols: a new family of glycosidase inhibitors and pharmacological chaperones.
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.
authors: Glycogroup, Deparment of Organic Chemistry, Graz University of Technology, 8010 Graz, Austria.
authors: Georg
authors: G
authors: Schitter
authors: Andreas J
authors: AJ
authors: Steiner
authors: Gerit
authors: G
authors: Pototschnig
authors: Elisabeth
authors: E
authors: Scheucher
authors: Martin
authors: M
authors: Thonhofer
authors: Chris A
authors: CA
authors: Tarling
authors: Stephen G
authors: SG
authors: Withers
authors: Katrin
authors: K
authors: Fantur
authors: Eduard
authors: E
authors: Paschke
authors: Don J
authors: DJ
authors: Mahuran
authors: Brigitte A
authors: BA
authors: Rigat
authors: Michael B
authors: MB
authors: Tropak
authors: Carina
authors: C
authors: Illaszewicz
authors: Robert
authors: R
authors: Saf
authors: Arnold E
authors: AE
authors: Stütz
authors: Tanja M
authors: TM
authors: Wrodnigg
mesh_terms: D002460:Cell Line; D003069:Coffee / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D004926:Escherichia coli / Q000201:enzymology; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D005696:Galactosidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016537:Gangliosidosis, GM1 / Q000188:drug therapy*; D054879:Halogenation; D006801:Humans; D007097:Imines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D012231:Rhizobium / Q000201:enzymology; D013402:Sugar Alcohols / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D003069:Coffee; D004791:Enzyme Inhibitors; D007097:Imines; D013402:Sugar Alcohols; D005696:Galactosidases