Chemical Synthesis and Antigenic Evaluation of Inner Core Oligosaccharides from Acinetobacter baumannii Lipopolysaccharide

Angew Chem Int Ed Engl. 2022 Jul 18;61(29):e202204420. doi: 10.1002/anie.202204420. Epub 2022 May 27.

Abstract

Acinetobacter baumannii is currently posing a serious threat to global health. Lipopolysaccharide (LPS) is a potent virulence factor of pathogenic Gram-negative bacteria. To explore the antigenic properties of A. baumannii LPS, four Kdo-containing inner core glycans from A. baumannii strain ATCC 17904 were synthesized. A flexible and divergent method based on the use of the orthogonally substituted α-Kdo-(2→5)-Kdo disaccharides was developed. Selective removal of different protecting groups in these key precursors and elongation of sugar chain via α-stereocontrolled coupling with 5,7-O-di-tert-butylsilylene or 5-O-benzoyl protected Kdo thioglycosides and 2-azido-2-deoxyglucosyl thioglycoside allowed efficient assembly of the target molecules. Glycan microarray analysis of sera from infected patients revealed that the 4,5-branched Kdo trimer was a potential antigenic epitope, which is attractive for further immunological research to develop carbohydrate vaccines against A. baumannii.

Keywords: Antigenicity; Carbohydrates; Glycosylation; Lipopolysaccharides; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter baumannii*
  • Carbohydrates
  • Disaccharides / chemistry
  • Humans
  • Lipopolysaccharides* / chemistry
  • Oligosaccharides / chemistry
  • Polysaccharides

Substances

  • Carbohydrates
  • Disaccharides
  • Lipopolysaccharides
  • Oligosaccharides
  • Polysaccharides