Tautomeric modification of GlcNAc-thiazoline.
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.
Knapp
Spencer
S
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
Abdo
Mohannad
M
Ajayi
Kehinde
K
Huhn
Richard A
RA
Emge
Thomas J
TJ
Kim
Eun Ju
EJ
Hanover
John A
JA
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
D004791:Enzyme Inhibitors; D005609:Free Radicals; C521910:GlcNAc-thiazoline; D013844:Thiazoles; D006596:Hexosaminidases; C110628:hexosaminidase C; D001619:beta-N-Acetylhexosaminidases; D005944:Glucosamine