title: Looking-glass synergistic pharmacological chaperones: DGJ and L-DGJ from the enantiomers of tagatose.
abstract: The enantiomers of tagatose are converted to L-DGJ [a noncompetitive inhibitor of human lysosome α-galactosidase A (α-Gal A), K(i) 38.5 μM] and DGJ [a competitive inhibitor of α-Gal A, K(i) 15.1 nM] in 66% yield. L-DGJ and DGJ provide the first examples of pharmacological chaperones that (a) are enantiomeric iminosugars and (b) have synergistic activity with implications for the treatment of lysosomal storage disorders and other protein deficiencies.
authors: Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, OX1 3TA, United Kingdom.
authors: Sarah F
authors: SF
authors: Jenkinson
authors: George W J
authors: GW
authors: Fleet
authors: Robert J
authors: RJ
authors: Nash
authors: Yuriko
authors: Y
authors: Koike
authors: Isao
authors: I
authors: Adachi
authors: Akihide
authors: A
authors: Yoshihara
authors: Kenji
authors: K
authors: Morimoto
authors: Ken
authors: K
authors: Izumori
authors: Atsushi
authors: A
authors: Kato
mesh_terms: D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D005898:Glass / Q000737:chemistry*; D006601:Hexoses / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D015394:Molecular Structure; D013237:Stereoisomerism; D000519:alpha-Galactosidase / Q000037:antagonists & inhibitors
chemical_list: D006601:Hexoses; D000519:alpha-Galactosidase; C030192:tagatose