Synthesis and characterisation of self-assembled and self-adjuvanting asymmetric multi-epitope lipopeptides of ovalbumin.

Synthesis and characterisation of self-assembled and self-adjuvanting asymmetric multi-epitope lipopeptides of ovalbumin.
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DOI:
10.1002/chem.201404997
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发表时间:
2015-01
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通讯作者:
Sharareh Eskandari;R. Stephenson;A. A. Fuaad-A.;S. Apte;D. Doolan;I. Toth
Sharareh Eskandari;R. Stephenson;A. A. Fuaad-A.;S. Apte;D. Doolan;I. Toth
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文献类型:
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作者:
Sharareh Eskandari;R. Stephenson;A. A. Fuaad-A.;S. Apte;D. Doolan;I. Toth

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Designing a lipopeptide (LP) vaccine with a specific asymmetric arrangement of epitopes may result in an improved display of antigens, increasing host-cell recognition and immunogenicity. This study aimed to synthesise and characterise the physicochemical properties of a library of asymmetric LP-based vaccine candidates that contained multiple CD4(+) and CD8(+) T-cell epitopes from the model protein antigen, ovalbumin. These fully synthetic vaccine candidates were prepared by microwave-assisted solid phase peptide synthesis. The C12 or C16 lipoamino acids were coupled to the N or C terminus of the OVA CD4 peptide epitope. The OVA CD4 LPs and OVA CD8 peptide constructs were then conjugated using azide-alkyne Huisgen cycloaddition to give multivalent synthetic vaccines. Physiochemical characterisation of these vaccines showed a tendency to self-assemble in aqueous media. Changes in lipid length and position induced self-assembly with significant changes to their morphology and secondary structure as shown by transmission electron microscopy and circular dichroism.