(Automated) Synthesis of Well-defined Staphylococcus Aureus Wall Teichoic Acid Fragments

Sara Ali, Astrid Hendriks, Rob van Dalen, Thomas Bruyning, Nico Meeuwenoord, Herman S. Overkleeft, Dmitri V. Filippov, Gijs A. van der Marel, Nina M. van Sorge, Jeroen D. C. Codée

Research output: Contribution to journalArticleAcademicpeer-review


Wall teichoic acids (WTAs) are important components of the cell wall of the opportunistic Gram-positive bacterium Staphylococcus aureus. WTAs are composed of repeating ribitol phosphate (RboP) residues that are decorated with d-alanine and N-acetyl-d-glucosamine (GlcNAc) modifications, in a seemingly random manner. These WTA-modifications play an important role in shaping the interactions of WTA with the host immune system. Due to the structural heterogeneity of WTAs, it is impossible to isolate pure and well-defined WTA molecules from bacterial sources. Therefore, here synthetic chemistry to assemble a broad library of WTA-fragments, incorporating all possible glycosylation modifications (α-GlcNAc at the RboP C4; β-GlcNAc at the RboP C4; β-GlcNAc at the RboP C3) described for S. aureus WTAs, is reported. DNA-type chemistry, employing ribitol phosphoramidite building blocks, protected with a dimethoxy trityl group, was used to efficiently generate a library of WTA-hexamers. Automated solid phase syntheses were used to assemble a WTA-dodecamer and glycosylated WTA-hexamer. The synthetic fragments have been fully characterized and diagnostic signals were identified to discriminate the different glycosylation patterns. The different glycosylated WTA-fragments were used to probe binding of monoclonal antibodies using WTA-functionalized magnetic beads, revealing the binding specificity of these WTA-specific antibodies and the importance of the specific location of the GlcNAc modifications on the WTA-chains.
Original languageEnglish
Pages (from-to)10461-10469
Number of pages9
JournalChemistry (Weinheim an der Bergstrasse, Germany)
Issue number40
Early online date2021
Publication statusPublished - 16 Jul 2021


  • antibodies
  • automated synthesis
  • gram-positive bacteria
  • ribitol phosphate
  • wall teichoic acids

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