OGA inhibition by GlcNAc-selenazoline

Bioorg Med Chem. 2010 Oct 1;18(19):7058-64. doi: 10.1016/j.bmc.2010.08.010. Epub 2010 Aug 11.

Abstract

The title compound, which differs from the powerful O-GlcNAcase (OGA) inhibitor GlcNAc-thiazoline only at the chalcogen atom (Se for S), is a much weaker inhibitor in a direct OGA assay. In human cells, however, the selenazoline shows comparable ability to induce hyper-O-GlcNAc-ylation, and the two show similar reduction of insulin-stimulated translocation of glucose transporter 4 in differentiated 3T3 adipocytes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Acetylglucosamine / analysis
  • Acetylglucosamine / metabolism
  • Adipocytes / metabolism
  • Amino Acid Sequence
  • Animals
  • Cell Differentiation / drug effects
  • Cell Line
  • Clostridium perfringens / enzymology
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Glucosamine / analogs & derivatives*
  • Glucosamine / chemical synthesis
  • Glucosamine / chemistry
  • Glucosamine / pharmacology
  • Glucose Transporter Type 4 / metabolism
  • Glycosylation
  • HeLa Cells
  • Humans
  • Insulin / pharmacology
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Sequence Alignment
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*
  • beta-N-Acetylhexosaminidases / antagonists & inhibitors*

Substances

  • Enzyme Inhibitors
  • GlcNAc-thiazoline
  • Glucose Transporter Type 4
  • Insulin
  • Thiazoles
  • hexosaminidase C
  • beta-N-Acetylhexosaminidases
  • Glucosamine
  • Acetylglucosamine