Chemical synthesis of intentionally misfolded homogeneous glycoprotein: a unique approach for the study of glycoprotein quality control

J Am Chem Soc. 2012 May 2;134(17):7238-41. doi: 10.1021/ja3013177. Epub 2012 Apr 17.


Biosynthesis of glycoproteins in the endoplasmic reticulum employs a quality control system, which discriminates and excludes misfolded malfunctional glycoproteins from a correctly folded one. As chemical tools to study the glycoprotein quality control system, we systematically synthesized misfolded homogeneous glycoproteins bearing a high-mannose type oligosaccharide via oxidative misfolding of a chemically synthesized homogeneous glycopeptide. The endoplasmic reticulum folding sensor enzyme, UDP-glucose:glycoprotein glucosyltransferase (UGGT), recognizes a specific folding intermediate, which exhibits a molten globule-like hydrophobic nature.

MeSH terms

  • Amino Acid Sequence
  • Endoplasmic Reticulum / enzymology*
  • Glucosyltransferases / metabolism*
  • Glycopeptides / chemical synthesis
  • Glycopeptides / chemistry
  • Glycopeptides / metabolism
  • Glycoproteins / chemical synthesis
  • Glycoproteins / chemistry*
  • Glycoproteins / metabolism*
  • Humans
  • Mannose / chemistry
  • Models, Molecular
  • Molecular Sequence Data
  • Oligosaccharides / chemistry
  • Oxidation-Reduction
  • Protein Folding*
  • Substrate Specificity


  • Glycopeptides
  • Glycoproteins
  • Oligosaccharides
  • Glucosyltransferases
  • mannosylglycoprotein 1,3-glucosyltransferase
  • Mannose