Dissertation

Synthesis of phosphodiester-containing bacterial cell wall components: teichoic acids, capsular polysaccharides and phosphatidyl glycerol analogues

Promotor: G.A. van der Marel, Co-promotor: J.D.C. Codée

Author: Daan van der Es
Date: 04 October 2016
Links: Thesis in Leiden Repository

This thesis describes the synthesis of various teichoic acid (TA)-fragments, capsular polysaccharide (CPS)-mimics and a toolbox of glycerol phosphate probes. Most of these molecules feature one or more phosphodiester functions, the introduction of which has been accomplished with phosphoramidite chemistry. The versatility of glycerol- and carbohydrate building blocks provided with a 2-cyanoethyl-protected phosphoramidite is illustrated by their application both in solution and in automated solid phase syntheses of TA and CPS oligomers as well as probes. The CPS-mimics are based on a polysaccharide present in the capsule of the gram negative bacterium Neisseria meningitidis, the pathogen that is the major cause of bacterial meningitis. The TA-fragments described in this thesis correspond to lipoteichoic acids (LTA) and wall teichoic acids (WTA) from Enterococcus faecalis and Enterococcus faecium, two commensal Gram-positive bacteria inhabiting the gastrointestinal tract. In both these bacterial families multi-drug-resistant strains have evolved and they are responsible for the majority of hospital-acquired infections. Enterococcal LTA generally consists of sn-glycerol-1-phosphate repeating units that can be decorated with carbohydrate- or D-alanyl appendages on the 2-OH of the glycerol moieties. The biosynthetic machinery of WTA is more complicated and can result in completely different structures.