Comparing Chemoenzymatic and Conventional Synthetic Strategies to Wall Teichoic Acid Peptidoglycan Fragments

In the cell wall of Gram-positive bacteria, wall teichoic acid (WTA) is an abundant and conserved virulence factor. WTAs are especially relevant to methicillin-resistant Staphylococcus aureus. Tremendous synthetic efforts have permitted investigations of the terminal end of this glycopolymer. However, the peptidoglycan (PG) linked end which utilizes a phosphodiester linkage, has been understudied due to its demanding synthesis. Two convergent routes, both involving a phospho-donor and an acceptor, were proposed and evaluated. In this work, synthesis of the more efficient route was carried out to obtain the phospho-donor and PG acceptor. Careful phosphoramidite coupling was utilized to establish the phosphodiester linkage between WTA and PG fragments. These WTA-PG conjugates will enable more complex studies between the host innate immune response and invading pathogens.