Total synthesis of Le(A)-LacNAc pentasaccharide as a ligand for Clostridium difficile toxin A

Org Biomol Chem. 2010 Jan 7;8(1):128-36. doi: 10.1039/b914193f. Epub 2009 Nov 13.

Abstract

The toxins TcdA and TcdB produced by the human pathogen Clostridium difficile gain entrance to host epithelial cells by recognizing cell-surface carbohydrate ligands. Inhibiting the attachment of these toxins to host cells has been proposed to be a viable therapy to treat C. difficile infections. Glycan array screening previously revealed that the Le(A)-LacNAc pentasaccharide binds strongly to TcdA. Here we report the efficient syntheses of the pentasaccharide and a structurally related tetrasaccharide motif. These compounds will be used to better define the carbohydrate-binding specificity of toxins from C. difficile, which will hopefully lead to the development of improved therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Toxins / metabolism*
  • Carbohydrate Sequence
  • Clostridioides difficile / metabolism*
  • Enterotoxins / metabolism*
  • Lewis Blood Group Antigens
  • Ligands
  • Models, Molecular
  • Molecular Sequence Data
  • Oligosaccharides / chemical synthesis
  • Oligosaccharides / chemistry*
  • Oligosaccharides / metabolism*
  • Protein Binding

Substances

  • Bacterial Toxins
  • Enterotoxins
  • Lewis Blood Group Antigens
  • Lewis a oligosaccharide
  • Ligands
  • Oligosaccharides
  • tcdA protein, Clostridium difficile