title: Tuning glycosidase inhibition through aglycone interactions: pharmacological chaperones for Fabry disease and GM1 gangliosidosis.
abstract: Competitive inhibitors of either α-galactosidase (α-Gal) or β-galactosidase (β-Gal) with high affinity and selectivity have been accessed by exploiting aglycone interactions with conformationally locked sp(2)-iminosugars. Selected compounds were profiled as potent pharmacological chaperones for mutant lysosomal α- and β-Gal associated with Fabry disease and GM(1) gangliosidosis.
authors.affiliation: Dpto. Química Orgánica, Fac. de Química, Universidad de Sevilla, c/ Professor García González 1, E-41012 Sevilla, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Aguilar-Moncayo
authors.forename: T
authors.initials: T
authors.lastname: Takai
authors.forename: K
authors.initials: K
authors.lastname: Higaki
authors.forename: T
authors.initials: T
authors.lastname: Mena-Barragán
authors.forename: Y
authors.initials: Y
authors.lastname: Hirano
authors.forename: K
authors.initials: K
authors.lastname: Yura
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Yu
authors.forename: H
authors.initials: H
authors.lastname: Ninomiya
authors.forename: M I
authors.initials: MI
authors.lastname: García-Moreno
authors.forename: S
authors.initials: S
authors.lastname: Ishii
authors.forename: Y
authors.initials: Y
authors.lastname: Sakakibara
authors.forename: K
authors.initials: K
authors.lastname: Ohno
authors.forename: E
authors.initials: E
authors.lastname: Nanba
authors.forename: C
authors.initials: C
authors.lastname: Ortiz Mellet
authors.forename: J M
authors.initials: JM
authors.lastname: García Fernández
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D000795:Fabry Disease / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D016537:Gangliosidosis, GM1 / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D050111:Imino Sugars / Q000737:chemistry; D008958:Models, Molecular; D009154:Mutation; D000519:alpha-Galactosidase / Q000037:antagonists & inhibitors* / Q000235:genetics; D001616:beta-Galactosidase / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D004791:Enzyme Inhibitors; D050111:Imino Sugars; D000519:alpha-Galactosidase; D001616:beta-Galactosidase