Chemical synthesis of the outer core oligosaccharide of Escherichia coli R3 and immunological evaluation

Org Biomol Chem. 2015 Apr 14;13(14):4321-30. doi: 10.1039/c5ob00177c. Epub 2015 Mar 12.

Abstract

Lipopolysaccharides (LPS), major virulence determinants in Gram-negative bacteria, are responsible for many pathophysiological responses and can elicit strong immune responses. In order to better understand the role of LPS in host-pathogen interactions and elucidate the immunogenic properties of LPS outer core oligosaccharides, an all α-linked Escherichia coli R3 outer core pentasaccharide was first synthesized with a propyl amino linker at the reducing end. This oligosaccharide was also covalently conjugated to a carrier protein (CRM197) via the reducing end propyl amino linker. Immunological analysis demonstrated that this glycoconjugate can elicit specific anti-pentasaccharide antibodies with in vitro bactericidal activity. These findings will contribute to the further exploration of this pentasaccharide antigen as a vaccine candidate.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / metabolism
  • Chemistry Techniques, Synthetic
  • Escherichia coli / chemistry*
  • Escherichia coli O157 / immunology
  • Female
  • Glycoconjugates / immunology
  • Immunoglobulin G / immunology
  • Immunoglobulin M / immunology
  • Mice
  • Mice, Inbred BALB C
  • Oligosaccharides / chemical synthesis*
  • Oligosaccharides / immunology*
  • Oligosaccharides / metabolism
  • Oxidation-Reduction

Substances

  • Bacterial Proteins
  • Glycoconjugates
  • Immunoglobulin G
  • Immunoglobulin M
  • Oligosaccharides
  • CRM197 (non-toxic variant of diphtheria toxin)