Synthesis and antibody-binding studies of a series of parasite fuco-oligosaccharides

Bioorg Med Chem. 2005 May 16;13(10):3553-64. doi: 10.1016/j.bmc.2005.02.009.

Abstract

Complex multifucosylated oligosaccharides are structural elements of glycoprotein and glycolipid subsets of larval, egg, and adult stages of Schistosoma, the parasitic worms that cause schistosomiasis, a serious disease affecting more than 200 million people in the tropics. The fucosylated structures are thought to play an important role in the immunology of schistosomiasis. Defined schistosomal oligosaccharides that enable immunological studies are difficult to obtain from natural sources. Therefore, we have chemically synthesized spacer-linked GlcNAc, Fucalpha1-3GlcNAc, Fucalpha1-2Fucalpha1-3GlcNAc, and Fucalpha1-2Fucalpha1-2Fucalpha1-3GlcNAc. This series of linear oligosaccharides was used to screen a library of anti-schistosome monoclonal antibodies by surface plasmon resonance spectroscopy. Interestingly, the reactive antibodies could be grouped according to their specificity for the different oligosaccharides tested, showing that these oligosaccharides form different immunological entities based on the number and linkage of the fucose residues. Subsequently, the thus defined monoclonal antibodies were used to visualize the expression of the corresponding oligosaccharide epitopes by adult Schistosoma mansoni worms.

MeSH terms

  • Animals
  • Antibodies, Helminth / immunology*
  • Antibodies, Helminth / metabolism
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / metabolism
  • Antibody Specificity
  • Carbohydrate Conformation
  • Cytotoxicity, Immunologic / immunology*
  • Epitopes / immunology
  • Fucose / immunology*
  • Hybridomas
  • Mice
  • Oligosaccharides* / chemical synthesis
  • Oligosaccharides* / immunology
  • Oligosaccharides* / metabolism
  • Schistosoma mansoni / growth & development*
  • Schistosoma mansoni / immunology*
  • Schistosomiasis mansoni / immunology
  • Schistosomiasis mansoni / metabolism
  • Surface Plasmon Resonance

Substances

  • Antibodies, Helminth
  • Antibodies, Monoclonal
  • Epitopes
  • Oligosaccharides
  • Fucose