title: Tautomeric modification of GlcNAc-thiazoline.
abstract: The potent O-GlcNAcase (OGA) inhibitor GlcNAc-thiazoline has been modified by buffer- or acylation-induced imine-to-enamine conversion and then electrophile or radical addition (Xn = D3, F, N3, OH, SMe, COCF3, CF3). Several functionalized GlcNAc-thiazolines show highly selective inhibition of OGA vs human hexosaminidase and thus have promise as tools for targeted investigations of OGA, an enzyme linked to diabetes and neurodegeneration. A new radical addition/fragmentation reaction of the N-(trifluoroacetyl)enamine has been discovered.
authors.affiliation: Department of Chemistry and Chemical Biology, Rutgers-The State University of New Jersey, 610 Taylor Road, Piscataway, New Jersey 08854, USA. spencer.knapp@rutgers.edu
authors.forename: Spencer
authors.initials: S
authors.lastname: Knapp
authors.forename: Mohannad
authors.initials: M
authors.lastname: Abdo
authors.forename: Kehinde
authors.initials: K
authors.lastname: Ajayi
authors.forename: Richard A
authors.initials: RA
authors.lastname: Huhn
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Emge
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Kim
authors.forename: John A
authors.initials: JA
authors.lastname: Hanover
mesh_terms: D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000528:radiation effects; D005609:Free Radicals / Q000138:chemical synthesis / Q000494:pharmacology / Q000528:radiation effects; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000528:radiation effects; D006596:Hexosaminidases / Q000037:antagonists & inhibitors; D006801:Humans; D007536:Isomerism; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000528:radiation effects; D001619:beta-N-Acetylhexosaminidases / Q000037:antagonists & inhibitors
chemical_list: D004791:Enzyme Inhibitors; D005609:Free Radicals; C521910:GlcNAc-thiazoline; D013844:Thiazoles; D006596:Hexosaminidases; C110628:hexosaminidase C; D001619:beta-N-Acetylhexosaminidases; D005944:Glucosamine