Glycosidase inhibition by ring-modified castanospermine analogues: tackling enzyme selectivity by inhibitor tailoring.
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.
Aguilar-Moncayo
Matilde
M
Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Profesor García González 1, 41012, Sevilla, (Spain).
Gloster
Tracey M
TM
Turkenburg
Johan P
JP
García-Moreno
M Isabel
MI
Ortiz Mellet
Carmen
C
Davies
Gideon J
GJ
García Fernández
José M
JM
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
D004791:Enzyme Inhibitors; D007212:Indolizines; D013890:Thiourea; D001617:beta-Glucosidase; C037806:castanospermine; D054836:Indolizidines