title: Glycosidase inhibition by ring-modified castanospermine analogues: tackling enzyme selectivity by inhibitor tailoring.
abstract: Synthesis of a panel of iso(thio)urea-type ring-modified castanospermine analogues bearing a freely mutarotating pseudoanomeric hydroxyl group results in tight-binding beta-glucosidase inhibitors with unusual binding signatures; the presence of an N-octyl substituent imparts a remarkable anomeric selectivity, promoting strong binding of the appropriate beta-anomer by the beta-glucosidase.
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Profesor García González 1, 41012, Sevilla, (Spain).
authors.forename: Matilde
authors.initials: M
authors.lastname: Aguilar-Moncayo
authors.forename: Tracey M
authors.initials: TM
authors.lastname: Gloster
authors.forename: Johan P
authors.initials: JP
authors.lastname: Turkenburg
authors.forename: M Isabel
authors.initials: MI
authors.lastname: García-Moreno
authors.forename: Carmen
authors.initials: C
authors.lastname: Ortiz Mellet
authors.forename: Gideon J
authors.initials: GJ
authors.lastname: Davies
authors.forename: José M
authors.initials: JM
authors.lastname: García Fernández
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007212:Indolizines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D013890:Thiourea / Q000031:analogs & derivatives / Q000737:chemistry; D001617:beta-Glucosidase / Q000037:antagonists & inhibitors*; D054836:Indolizidines
chemical_list: D004791:Enzyme Inhibitors; D007212:Indolizines; D013890:Thiourea; D001617:beta-Glucosidase; C037806:castanospermine; D054836:Indolizidines