Synthesis of E. faecium wall teichoic acid fragments

Daan van der Es; Nadia A Groenia; Diana Laverde; Herman S Overkleeft; Johannes Huebner; Gijsbert A van der Marel; Jeroen D C Codée

doi:10.1016/j.bmc.2016.03.019

Synthesis of E. faecium wall teichoic acid fragments

Bioorg Med Chem. 2016 Sep 1;24(17):3893-3907. doi: 10.1016/j.bmc.2016.03.019. Epub 2016 Mar 9.

Authors

Daan van der Es¹, Nadia A Groenia¹, Diana Laverde², Herman S Overkleeft¹, Johannes Huebner², Gijsbert A van der Marel³, Jeroen D C Codée⁴

Affiliations

¹ Leiden Institute of Chemistry, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands.
² Division of Pediatric Infectious Diseases, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University, Munich, Germany.
³ Leiden Institute of Chemistry, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands. Electronic address: marel_g@chem.leidenuniv.nl.
⁴ Leiden Institute of Chemistry, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands. Electronic address: jcodee@chem.leidenuniv.nl.

PMID: 26993744
DOI: 10.1016/j.bmc.2016.03.019

Abstract

The first synthesis of different Enterococcus faecium wall teichoic acid (WTA) fragments is presented. The structure of these major cell wall components was elucidated recently and it was shown that these glycerolphosphate (GroP) based polymers are built up from -6-(GalNAc-α(1-3)-GalNAc-β(1-2)-GroP)- repeating units. We assembled WTA fragments up to three repeating units in length, in two series that differ in the stereochemistry of the glycerolphosphate moiety. The key GalNAc-GalNAc-GroP synthons, required for the synthesis, were generated from galactosazide building blocks that were employed in highly stereoselective glycosylation reactions to furnish both the α- and β-configured linkages. By comparing the NMR spectra of the synthesized fragments with the isolated material it appears that the hereto undefined stereochemistry of the glycerol phosphate moiety is sn-glycerol-3-phosphate. The generated fragments will be valuable tools to study their immunological activity at the molecular level.

Keywords: Carbohydrate; E. faecium; Glycosylation; Phosphoramidite; Wall teichoic acid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carbohydrate Sequence
Cell Wall / chemistry*
Enterococcus faecium / chemistry*
Stereoisomerism
Teichoic Acids / chemical synthesis*

Substances

Teichoic Acids