N-Acetylhexosaminidase inhibitory properties of C-1 homologated GlcNAc- and GalNAc-thiazolines.
Several C-1 homologated GlcNAc- and GalNAc-thiazolines, as well as a related GalNAc-thiazole, have been prepared. The compounds are analogues of GlcNAc-thiazoline, a potent transition-state-mimicking inhibitor of retaining beta-N-acetylglycosaminidases. Kinetic evaluation of these fused pyranose-heterocycles against the bacterial N-acetylhexosaminidase SpHex suggests active site steric restrictions around the substrate anomeric carbon.
Amorelli
Benjamin
B
Department of Chemistry & Chemical Biology, Rutgers, The State University of New Jersey, 610 Taylor Road, Piscataway, NJ 08854, USA.
Yang
Chunhua
C
Rempel
Brian
B
Withers
Stephen G
SG
Knapp
Spencer
S
D001665:Binding Sites; D002240:Carbohydrate Sequence; D002244:Carbon / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D005690:Galactose / Q000138:chemical synthesis / Q000494:pharmacology*; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D007700:Kinetics; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology; D013379:Substrate Specificity; D013844:Thiazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D001619:beta-N-Acetylhexosaminidases / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; C521910:GlcNAc-thiazoline; D010880:Piperidines; D013844:Thiazoles; D002244:Carbon; D001619:beta-N-Acetylhexosaminidases; D005944:Glucosamine; D005690:Galactose