Design and Synthesis of Lipopeptide–Carbohydrate Assembled Multivalent Vaccine Candidates Using Native Chemical Ligation

Wei Zhong; Mariusz Skwarczynski; Yoshio Fujita; Pavla Simerska; Michael F. Good; Istvan Toth

doi:10.1071/CH09065

RESEARCH ARTICLE

Design and Synthesis of Lipopeptide–Carbohydrate Assembled Multivalent Vaccine Candidates Using Native Chemical Ligation

Wei Zhong ^A , Mariusz Skwarczynski ^A , Yoshio Fujita ^A , Pavla Simerska ^A , Michael F. Good ^B and Istvan Toth ^A ^C

+ Author Affiliations

- Author Affiliations

^A The University of Queensland, School of Chemistry and Molecular Biosciences, St. Lucia, Qld 4072, Australia.

^B Queensland Institute of Medical Research, Herston, Qld 4029, Australia.

^C Corresponding author. Email: i.toth@uq.edu.au

Australian Journal of Chemistry 62(9) 993-999 https://doi.org/10.1071/CH09065
Submitted: 2 February 2009 Published: 17 September 2009

Abstract

Development of a synthetic vaccine against group A streptococcal infection is increasingly paramount due to the induction of autoimmunity by the main virulent factor – M protein. Peptide vaccines, however, are generally poorly immunogenic, necessitating administration with carriers and adjuvants. One of the promising approaches to deliver antigenic peptides is to assemble peptides on a suitable template which directs the attached peptides to form a well defined tertiary structure. For self-adjuvanting human vaccines, the conjugation of immunostimulatory lipids has been demonstrated as a potentially safe method. This study describes the design and optimized synthesis of two lipopeptide conjugated carbohydrate templates and the assembling of peptide antigens. These lipopeptide–carbohydrate assembled multivalent vaccine candidates were obtained in high yield and purity when native chemical ligation was applied. Circular dichroism studies indicated that the template-assembled peptides form four α-helix bundles. The developed technique extends the use of carbohydrate templates and lipopeptide conjugates for producing self-adjuvanting and topology-controlled vaccine candidates.

Acknowledgements

This work was supported by the National Health and Medical Research Council (NHMRC) of Australia and the Australian National Heart Foundation (NHF). The author would like to acknowledge Chris Wood (University of Queensland, SCMB) for LC-ESI-MS analysis.

References

Design and Synthesis of Lipopeptide–Carbohydrate Assembled Multivalent Vaccine Candidates Using Native Chemical Ligation

Abstract

Acknowledgements

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