Synthesis of Lewis X-O-Core-1 threonine: A building block for O-linked Lewis X glycopeptides

Carbohydr Res. 2017 Nov 27;452:47-53. doi: 10.1016/j.carres.2017.10.002. Epub 2017 Oct 10.

Abstract

LewisX (LeX) is a branched trisaccharide Galβ1→4(Fucα1→3)GlcNAc that is expressed on many cell surface glycoproteins and plays critical roles in innate and adaptive immune responses. However, efficient synthesis of glycopeptides bearing LeX remains a major limitation for structure-function studies of the LeX determinant. Here we report a total synthesis of a LeX pentasaccharide 1 using a regioselective 1-benzenesulfinyl piperidine/triflic anhydride promoted [3 + 2] glycosylation. The presence of an Fmoc-threonine amino acid facilitates incorporation of the pentasaccharide in solid phase peptide synthesis, providing a route to diverse O-linked LeX glycopeptides. The described approach is broadly applicable to the synthesis of a variety of complex glycopeptides containing O-linked LeX or sialyl LewisX (sLeX).

MeSH terms

  • Amino Acids / chemistry
  • Glycopeptides / chemical synthesis*
  • Glycopeptides / chemistry*
  • Glycosylation
  • Oligosaccharides / chemistry*
  • Solid-Phase Synthesis Techniques / methods
  • Threonine / chemistry*

Substances

  • Amino Acids
  • Glycopeptides
  • Oligosaccharides
  • Threonine