GlcNAc-Thiazoline conformations.
The title compound, a powerful inhibitor of retaining N-acetylhexosaminidases, can move freely among three pyranose solution conformations of similar energy-two twist boats and the (4)C(1) chair-as revealed by NMR, calculational, and crystallographic studies. It binds in the enzyme active site only in the pseudo-(4)C(1) conformation, however, in which it most closely resembles the hypothetical bound substrate transition state, a (4)E sofa that is approximately trigonal bipyramidal at the anomeric carbon.
Knapp
Spencer
S
Department of Chemistry and Chemical Biology, Rutgers The State University of New Jersey, Piscataway, NJ 08854, USA. spencer.knapp@rutgers.edu
Fash
David
D
Abdo
Mohannad
M
Emge
Thomas J
TJ
Rablen
Paul R
PR
D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D013816:Thermodynamics; D013844:Thiazoles / Q000737:chemistry*; D001619:beta-N-Acetylhexosaminidases / Q000037:antagonists & inhibitors / Q000737:chemistry
D004791:Enzyme Inhibitors; C521910:GlcNAc-thiazoline; D013844:Thiazoles; C110628:hexosaminidase C; D001619:beta-N-Acetylhexosaminidases; D005944:Glucosamine