Synthesis and biological evaluation of a chitobiose-based peptide N-glycanase inhibitor library

J Org Chem. 2009 Jan 16;74(2):605-16. doi: 10.1021/jo801906s.

Abstract

Peptide N-glycanase (PNGase), the enzyme responsible for the deglycosylation of N-linked glycoproteins, has an active site related to that of cysteine proteases. Chitiobiose was equipped with electrophilic traps often used in cysteine protease inhibitors, and the resulting compounds were evaluated as PNGase inhibitors. We found that the electrophilic trap of the inhibitor has a great influence on the potency of the compounds with the chloromethyl ketone inhibitor being the first potent C-glycoside-based PNGase inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / chemical synthesis
  • Acetamides / chemistry
  • Acetamides / pharmacology
  • Cell Line
  • Cysteine Proteinase Inhibitors / chemistry
  • Disaccharides / chemistry*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / antagonists & inhibitors*
  • Small Molecule Libraries / chemical synthesis*
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Substrate Specificity

Substances

  • Acetamides
  • Cysteine Proteinase Inhibitors
  • Disaccharides
  • Enzyme Inhibitors
  • Small Molecule Libraries
  • chitobiose
  • acetamide
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase