Convenient synthesis of a sialylglycopeptide-thioester having an intact and homogeneous complex-type disialyl-oligosaccharide

Carbohydr Res. 2006 Jul 24;341(10):1333-40. doi: 10.1016/j.carres.2006.04.037. Epub 2006 May 15.


Access to glycopeptides with C-terminal thioester functionality is essential for the synthesis of large glycopeptides and glycoproteins through the use of native chemical ligation. Toward that end, we have developed a concise method for the synthesis of a glycopeptide thioester having an intact complex-type dibranched disialyl-oligosaccharide. The synthesis employed a coupling reaction between benzylthiol and a free carboxylic acid at the C-terminus of a glycopeptide in which the peptide side chains are protected. After construction of glycopeptide on the HMPB-PEGA resin through the Fmoc-strategy, the protected glycopeptide was released upon treatment with acetic acid/trifluoroethanol and then the C-terminal carboxylic acid was coupled with benzylthiol at -20 degrees C in DMF. For this coupling, PyBOP/DIPEA was found to be the best for the formation of the thioester, while avoiding racemization. Finally, the protecting groups were removed in good yield with 95% TFA, thus affording a glycopeptide-thioester having an intact and homogeneous complex-type disialyl-oligosaccharide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Glycopeptides / chemical synthesis*
  • Oligosaccharides / chemical synthesis*
  • Sialic Acids / chemical synthesis*
  • Stereoisomerism
  • Sulfur Compounds / chemical synthesis


  • Glycopeptides
  • Oligosaccharides
  • Sialic Acids
  • Sulfur Compounds