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Investigating the affinity of poly tert-butyl acrylate toward Toll-Like Receptor 2

1 School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia
2 Helwan University, Faculty of Pharmacy, Pharmaceutical Organic Chemistry Department, Ein Helwan, Egypt
3 Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia
4 Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia
5 School of Pharmacy, The University of Queensland, Brisbane, QLD 4072, Australia

Despite the high safety profile of peptide-based vaccines over conventional counterparts, the inability of small peptides to produce a strong immune response represents the main obstacle for the development of these types of vaccines. Introducing a self-adjuvanting moiety such as poly tert-butyl acrylate can overcome this problem. However, the mode of action of this polymer to produce the desired humoral and/or cellular immune response is still unknown. An AlphaScreen assay along with the cell-free expression technique were employed to evaluate the affinity of this polymer toward toll-like receptor 2 (TLR2) for stimulation of innate immunity. In this study, B-cell epitope, J14, derived from the M protein of group A streptococcus (GAS) was used in conjugation with the poly tert-butyl acrylate as well as a biotin moiety. Pam2Cys analogue, the potent TLR2 agonist, was synthesized and used as a positive control in this work. The AlphaScreen assay showed the inability of polymer to bind to TLR2, while the Pam2Cys displayed very strong binding to TLR2 as expected. This result indicated that poly tert-butyl acrylate does not express its immunogenic effects through recognition by TLR2 and therefore further studies are required to determine its mode of action.
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Keywords TLR2 agonists; poly tert-butyl acrylate; vaccines; AlphaScreen assay; adjuvant

Citation: Waleed M. Hussein, Phil M. Choi, Cheng Zhang, Emma Sierecki, Wayne Johnston, Zhongfan Jia, Michael J. Monteiro, Mariusz Skwarczynski, Yann Gambin, Istvan Toth. Investigating the affinity of poly tert-butyl acrylate toward Toll-Like Receptor 2. AIMS Allergy and Immunology, 2018, 2(3): 141-147. doi: 10.3934/Allergy.2018.3.141

References

  • 1. Purcell AW, McCluskey J, Rossjohn J (2007) More than one reason to rethink the use of peptides in vaccine design. Nat Rev Drug Discov 6: 404–414.    
  • 2. Pruksakorn S, Currie B, Brandt E, et al. (1994) Identification of T-cell autoepitopes that cross-react with the C-terminal segment of the M-protein of group-a streptococci. Int Immunol 6: 1235–1244.    
  • 3. Kotb M, Courtney HS, Dale JB, et al. (1989) Cellular and biochemical responses of human Lymphocytes-T stimulated with streptococcal-m proteins. J Immunol 142: 966–970.
  • 4. Hayman WA, Brandt ER, Relf WA, et al. (1997) Mapping the minimal murine T cell and B cell epitopes within a peptide vaccine candidate from the conserved region of the M protein of group A streptococcus. Int Immunol 9: 1723–1733.    
  • 5. Skwarczynski M, Zaman M, Urbani CN, et al. (2010) Polyacrylate dendrimer nanoparticles: a self-adjuvanting vaccine delivery system. Angew Chem Int Edit 49: 5742–5745.    
  • 6. Ahmad FAA, Jia Z, Zaman M, et al. (2014) Polymer-peptide hybrids as a highly immunogenic single-dose nanovaccine. Nanomedicine 9: 35–43.    
  • 7. Chandrudu S, Bartlett S, Khalil ZG, et al. (2016) Linear and branched polyacrylates as a delivery platform for peptide-based vaccines. Ther Deliv 7: 601–609.    
  • 8. Zaman M, Skwarczynski M, Malcolm JM, et al. (2011) Self-adjuvanting polyacrylic nanoparticulate delivery system for group A streptococcus (GAS) vaccine. Nanomed-Nanotechnol 7: 168–173.    
  • 9. Hussein WM, Liu TY, Jia Z, et al. (2016) Multiantigenic peptide-polymer conjugates as therapeutic vaccines against cervical cancer. Bioorgan Med Chem 24: 4372–4380.    
  • 10. Liu TY, Hussein WM, Giddam AK, et al. (2015) Polyacrylate-based delivery system for self-adjuvanting anticancer peptide vaccine. J Med Chem 58: 888–896.    
  • 11. Liu TY, Hussein WM, Jia Z, et al. (2013) Self-adjuvanting polymer-peptide conjugates as therapeutic vaccine candidates against cervical cancer. Biomacromolecules 14: 2798–2806.    
  • 12. Liu TY, Giddam AK, Hussein WM, et al. (2015) Self-adjuvanting therapeutic peptide-based vaccine induce cd8(+) cytotoxic t lymphocyte responses in a murine human papillomavirus tumor model. Curr Drug Deliv 12: 3–8.    
  • 13. Akira S, Takeda K, Kaisho T (2001) Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2: 675–680.    
  • 14. Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124: 783–801.    
  • 15. Iwasaki A, Medzhitov R (2004) Toll-like receptor control of the adaptive immune responses. Nat Immunol 5: 987–995.    
  • 16. Skwarczynski M, Dougall AM, Khoshnejad M, et al. (2012) Peptide-based subunit vaccine against hookworm infection. PLoS One 7: e46870.    
  • 17. Abdel-Aal ABM, Al-Isae K, Zaman M, et al. (2011) Simple synthetic toll-like receptor 2 ligands. Bioorg Med Chem Lett 21: 5863–5865.    
  • 18. Abdel-Aal ABM, El-Naggar D, Zaman M, et al. (2012) Design of fully synthetic, self-adjuvanting vaccine incorporating the tumor-associated carbohydrate tn antigen and lipoamino acid-based Toll-like Receptor 2 ligand. J Med Chem 55: 6968–6974.    
  • 19. Miyake K (2007) Innate immune sensing of pathogens and danger signals by cell surface Toll-like receptors. Semin Immunol 19: 3–10.    
  • 20. Tapping RI (2009) Innate immune sensing and activation of cell surface Toll-like receptors. Semin Immunol 21: 175–184.    
  • 21. Moyle PM, Toth I (2008) Self-adjuvanting lipopeptide vaccines. Curr Med Chem 15: 506–516.    
  • 22. Eriksson EM, Jackson DC (2007) Recent advances with TLR2-targeting lipopeptide-based vaccines. Curr Protein Pept Sci 8: 412–417.    
  • 23. Hussein WM, Choi PM, Zhang C, et al. (2017) Evaluation of lipopeptides as Toll-like Receptor 2 Ligands. Curr Drug Deliv 14: 935–943.
  • 24. Gagoski D, Mureev S, Giles N, et al. (2015) Gateway-compatible vectors for high-throughput protein expression in pro- and eukaryotic cell-free systems. J Biotechnol 195: 1–7.    
  • 25. Kovtun O, Mureev S, Jung W, et al. (2011) Leishmania cell-free protein expression system. Methods 55: 58–64.    
  • 26. Mureev S, Kovtun O, Nguyen UTT, et al. (2009) Species-independent translational leaders facilitate cell-free expression. Nat Biotechnol 27: 747–752.    
  • 27. Tan ACL, Mifsud EJ, Zeng WG, et al. (2012) Intranasal administration of the TLR2 agonist Pam2Cys provides rapid protection against influenza in mice. Mol Pharm 9: 2710–2718.    
  • 28. Zeng WG, Eriksson E, Chua B, et al. (2010) Structural requirement for the agonist activity of the TLR2 ligand Pam2Cys. Amino Acids 39: 471–480.    

 

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