Aglycon specificity profiling of alpha-glucosidases using synthetic probes

Bioorg Med Chem Lett. 2005 Mar 1;15(5):1489-92. doi: 10.1016/j.bmcl.2004.12.086.

Abstract

We designed and synthesized hydrogen bond based probes 1-8 with the exception of known glycosidase inhibition mechanisms, and aglycon specificity of 11 different sources of alpha-glucosidases were investigated using their probes. Probe 4 (2,6-anhydro-1-deoxy-1-[(1-oxopentyl-5-hydroxy)amino]-D-glycero-D-ido-heptitol) showed a potent inhibition of S. cerevisiae alpha-glucosidase among all alpha-glucosidases. Probe 4 was found to be a competitive inhibitor for S. cerevisiae alpha-glucosidase with Ki 0.13 mM.

MeSH terms

  • 1-Deoxynojirimycin
  • Animals
  • Drug Design
  • Geobacillus stearothermophilus / drug effects
  • Geobacillus stearothermophilus / enzymology
  • Glucosamine / analogs & derivatives*
  • Glucosamine / chemistry
  • Glycoside Hydrolase Inhibitors*
  • Heptoses / chemical synthesis
  • Heptoses / chemistry
  • Heptoses / pharmacology*
  • Hydrogen Bonding
  • Microbial Sensitivity Tests
  • Molecular Conformation
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / enzymology
  • Structure-Activity Relationship
  • Substrate Specificity / drug effects

Substances

  • Glycoside Hydrolase Inhibitors
  • Heptoses
  • deoxynojirimycine
  • 1-Deoxynojirimycin
  • Glucosamine