Design and synthesis of lipopeptide-carbohydrate assembled multivalent vaccine candidates using native chemical ligation
Author(s)
Zhong, Wei
Skwarczynski, Mariusz
Fujita, Yoshio
Simerska, Pavla
F. Good, Michael
Toth, Istvan
Griffith University Author(s)
Year published
2009
Metadata
Show full item recordAbstract
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 ...
View more >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 a-helix bundles. The developed technique extends the use of carbohydrate templates and lipopeptide conjugates for producing self-adjuvanting and topology-controlled vaccine candidates.
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View more >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 a-helix bundles. The developed technique extends the use of carbohydrate templates and lipopeptide conjugates for producing self-adjuvanting and topology-controlled vaccine candidates.
View less >
Journal Title
Australian Journal of Chemistry
Volume
62
Issue
9
Subject
Infectious Diseases
Chemical Sciences