Zwitterionic Phosphodiester-Substituted Neoglycoconjugates as Ligands for Antibodies and Acute Phase Proteins

ACS Chem Biol. 2020 Feb 21;15(2):369-377. doi: 10.1021/acschembio.9b00794. Epub 2020 Jan 29.

Abstract

Zwitterionic modifications of glycans, such as phosphorylcholine and phosphoethanolamine, are known from a range of prokaryotic and eukaryotic species and are recognized by mammalian antibodies and pentraxins; however, defined saccharide ligands modified with these zwitterionic moieties for high-throughput studies are lacking. In this study, we prepared and tested example mono- and disaccharides 6-substituted with either phosphorylcholine or phosphoethanolamine as bovine serum albumin neoglycoconjugates or printed in a microarray format for subsequent assessment of their binding to lectins, pentraxins, and antibodies. C-Reactive protein and anti-phosphorylcholine antibodies bound specifically to ligands with phosphorylcholine, but recognition by concanavalin A was abolished or decreased as compared with that to the corresponding nonzwitterionic compounds. Furthermore, in array format, the phosphorylcholine-modified ligands were recognized by IgG and IgM in sera of either non-infected or nematode-infected dogs and pigs. Thereby, these new compounds are defined ligands which allow the assessment of glycan-bound phosphorylcholine as a target of both the innate and adaptive immune systems in mammals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascariasis / diagnosis
  • Ascariasis / veterinary
  • Ascaris
  • C-Reactive Protein / metabolism*
  • Carbohydrate Sequence
  • Cattle
  • Dirofilaria immitis
  • Dirofilariasis / diagnosis
  • Dogs
  • Ethanolamines / chemical synthesis
  • Ethanolamines / immunology
  • Ethanolamines / metabolism
  • Glycoconjugates / chemical synthesis
  • Glycoconjugates / immunology
  • Glycoconjugates / metabolism*
  • Humans
  • Immunoglobulin G / immunology*
  • Immunoglobulin M / immunology*
  • Ligands
  • Phosphorylcholine / analogs & derivatives
  • Phosphorylcholine / immunology
  • Phosphorylcholine / metabolism
  • Protein Binding
  • Serum Albumin, Bovine / chemistry
  • Serum Amyloid P-Component / metabolism*
  • Swine

Substances

  • Ethanolamines
  • Glycoconjugates
  • Immunoglobulin G
  • Immunoglobulin M
  • Ligands
  • Serum Amyloid P-Component
  • Phosphorylcholine
  • Serum Albumin, Bovine
  • phosphorylethanolamine
  • C-Reactive Protein