Poster Presentation 8th Modern Solid Phase Peptide Synthesis & Its Applications Symposium 2022

Development of glycotopes to protect against streptococcus pyogenes using solid-phase synthesis (#125)

Asmaa Mahmoud 1 , Istvan Toth 2 3 4 , Rachel Stephenson 4
  1. School of Chemistry and Molecular Biosciences, The University of Queensland, saint lucia, Queensland, Australia
  2. School of Pharmacy, Australia, The University of Queensland, Woolloongabba, Queensland, Australia
  3. Institute for Molecular Biosciences, The University of Queensland, saint lucia, Queensland, Australia
  4. School of Chemistry and Molecular Biosciences, The University of Queensland, saint lucia, Queensland, Australia

Introduction: S. pyogenes is a widespread primary infective agent in humans and causes ~700 million human infections each year, beginning from mild streptococcal pharyngitis (strep throat) to invasive streptococcal pneumonia, necrotizing fasciitis, toxic shock syndrome, and myositis [1]. In addition to causing post-streptococcal sequelae, such as rheumatic heart disease (RHD), rheumatic fever (RF) and acute glomerulonephritis. The estimated total economic burden of GAS-induced disease in Australia, according to 2015 birth rates, was more than 44 million AUD with GAS-induced heart diseases, RF and RHD contributed more than 16 million AUD [2, 3]. Carbohydrate-based vaccines have been proven to be the most promising subunit vaccine candidates, as the bacterial glycan pattern are different from that of the mammalian cells and show more conservancy amongst pathogen serotypes than that of the protein components. In this work, we implemented the outcomes of the recent contributions of reverse vaccinology to develop a glycan-based subunit vaccine against S. pyogenes. We adapted a facile method for the synthesis of the glycotopes of S. pyogenes to be later conjugated to self-adjuvanting lipo-peptide and cyclic peptides.

Methods: We have adapted a robust method to prepare the glycotope of S. pyogenes which is a blend of liquid-phase and solid-phase glycan synthesis requiring a single orthogonally-protected rhamnosyl monomer (Figure 1).

 

Results: Orthogonally protected rhamnosyl monomer building blocks have been successfully prepared and the structure have been confirmed by NMR and mass spectrometry analysis. The scheme for glycotope synthesis via solid-phase glycan synthesis will also be presented.   

 

  1. 1. Nowak, R., Flesh-eating bacteria: Not new, but still worrisome. Science, 1994. 264(5166): p. 1665. 2. Cannon, J.W., et al., An economic case for a vaccine to prevent group A streptococcus skin infections. Vaccine, 2018. 36(46): p. 6968-6978. 3. Roberts, K., et al., Echocardiographic screening for rheumatic heart disease in indigenous Australian children: A cost–utility analysis. Journal of the American Heart Association, 2017. 6(3): p. e004515.