Abstract
One of the factors responsible for the poor immunogenicity of synthetic peptide antigens is the lack of conformational integrity. Embedding the minimal epitopes in helix-promoting peptide sequences has successfully enhanced the immunogenicity of the epitopes derived from the α-helical regions of the M protein of group A streptococci (Streptococcus pyogenes, GAS). However, the introduction of “foreign” peptide sequences is believed to have an unfavourable impact on the antigen specificity. In the current study, we employed a non-peptide approach, using topological carbohydrate templates, to induce helical conformation of the peptide antigens. Utilized together with the advances of the lipid core peptide system and chemoselective ligation, five GAS vaccine candidates incorporating the minimal epitope J14i (ASREAKKQVEKALE) were synthesized with high purity. Circular dichroism studies indicated that the template-assembled peptides formed α-helix bundles. This atom-economic strategy also reduces the complexity and cost of vaccine production by simply reducing the peptide epitope size.
Keywords: Conformational mimetic, carbohydrate template, self-adjuvanting lipopeptide vaccine, lipid core peptide, α-helicity, group A streptococcus, infectious disease
Current Drug Delivery
Title: Development of Conformational Mimetics of Conserved Streptococcus Pyogenes Minimal Epitope as Vaccine Candidates
Volume: 6 Issue: 5
Author(s): Wei Zhong, Mariusz Skwarczynski and Istvan Toth
Affiliation:
Keywords: Conformational mimetic, carbohydrate template, self-adjuvanting lipopeptide vaccine, lipid core peptide, α-helicity, group A streptococcus, infectious disease
Abstract: One of the factors responsible for the poor immunogenicity of synthetic peptide antigens is the lack of conformational integrity. Embedding the minimal epitopes in helix-promoting peptide sequences has successfully enhanced the immunogenicity of the epitopes derived from the α-helical regions of the M protein of group A streptococci (Streptococcus pyogenes, GAS). However, the introduction of “foreign” peptide sequences is believed to have an unfavourable impact on the antigen specificity. In the current study, we employed a non-peptide approach, using topological carbohydrate templates, to induce helical conformation of the peptide antigens. Utilized together with the advances of the lipid core peptide system and chemoselective ligation, five GAS vaccine candidates incorporating the minimal epitope J14i (ASREAKKQVEKALE) were synthesized with high purity. Circular dichroism studies indicated that the template-assembled peptides formed α-helix bundles. This atom-economic strategy also reduces the complexity and cost of vaccine production by simply reducing the peptide epitope size.
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Cite this article as:
Zhong Wei, Skwarczynski Mariusz and Toth Istvan, Development of Conformational Mimetics of Conserved Streptococcus Pyogenes Minimal Epitope as Vaccine Candidates, Current Drug Delivery 2009; 6 (5) . https://dx.doi.org/10.2174/156720109789941650
DOI https://dx.doi.org/10.2174/156720109789941650 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |
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