Efficient synthesis of glycopeptide-α-thioesters with a high-mannose type oligosaccharide by means of tert-Boc-solid phase peptide synthesis

Carbohydr Res. 2012 Dec 15:364:41-8. doi: 10.1016/j.carres.2012.10.011. Epub 2012 Oct 23.

Abstract

High-mannose type oligosaccharides consist of nine mannose and two N-acetylglucosamine residues (Man(9)GlcNAc(2):M9) and play an important role in protein folding processes in the endoplasmic reticulum. A highly efficient preparation method of this asparaginyl-M9-oligosaccharide from hen egg yolk was established by a two-step proteolysis with commercially available proteases and subsequent purification using high performance liquid chromatography (HPLC). To avoid the hydrolysis of the desired M9-oligosaccharide during the proteolysis steps, several commercially available proteases were screened for their contamination with mannosidases. The α-amino group of the resultant H(2)N-Asn-(M9-oligosaccharide)-OH was protected with 9-fluorenylmethyloxycarbonyl (Fmoc) group for convenient separation by HPLC. The structure of Fmoc-Asn-(M9-oligosaccharide)-OH thus obtained was confirmed by ESI-MS spectrometry and several NMR experiments. Using this Fmoc-Asn-(M9-oligosaccharide)-OH, the synthesis of the M9-glycopeptide-α-thioester was demonstrated by means of tert-Boc-solid phase peptide synthesis. These tert-Boc conditions afforded the M9-glycopeptide-α-thioester in moderate yield.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asparagine / chemistry
  • Chickens
  • Chromatography, High Pressure Liquid
  • Egg Yolk / chemistry
  • Enzyme Activation
  • Esters / chemistry
  • Esters / isolation & purification
  • Fluorenes / chemistry
  • Glycoproteins / chemistry
  • Glycoproteins / isolation & purification*
  • Magnetic Resonance Spectroscopy
  • Mannans / chemistry
  • Mannans / isolation & purification
  • Mannose / chemistry*
  • Mannosidases / chemistry
  • Molecular Structure
  • Oligosaccharides / chemistry*
  • Oligosaccharides / isolation & purification
  • Peptide Hydrolases / chemistry
  • Protein Folding
  • Proteolysis*
  • Solid-Phase Synthesis Techniques / methods*
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • 9-fluorenylmethoxycarbonyl
  • Esters
  • Fluorenes
  • Glycoproteins
  • Mannans
  • Oligosaccharides
  • mannosyl(9)-N-acetylglucosamine2
  • Asparagine
  • Mannosidases
  • Peptide Hydrolases
  • Mannose