Synthetic Approaches to Multivalent Lipopeptide Dendrimers Containing Cyclic Disulfide Epitopes of Foot-and-Mouth Disease Virus
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- 作者：Eliandre de Oliveira ; Judit Villé ; n ; Ernest Giralt ; and David Andreu
- 刊名：Bioconjugate Chemistry
- 出版年：2003
- 出版时间：January 2003
- 年：2003
- 卷：14
- 期：1
- 页码：144 - 152
- 全文大小：147K
- 年卷期：v.14,no.1(January 2003)
- ISSN：1520-4812
文摘
The synthesis of a multiantigenic peptide dendrimer incorporating four copies of a cyclic disulfideepitope has been undertaken. Since standard chemoselective ligation procedures involving thioetherformation are inadvisable in the presence of a preformed disulfide, conjugation through a peptidebond between the lipidated branched lysine scaffold and a suitably protected version of the cyclicdisulfide has been used instead. Several synthetic approaches to the partially protected cyclic disulfidepeptide have been explored. The most effective involves building a minimally protected version of thepeptide by Boc solid phase synthesis, using fluorenyl-based anchorings and cysteine protecting groups.Peptide-resin cleavage and cysteine deprotection/oxidation are performed simultaneously by base-promoted elimination. The cyclic disulfide epitope is readily obtained in sufficient amounts by thisprocedure and subsequently incorporated to the lipidated lysine core by peptide bond formation insolution. A final acid deprotection step in anhydrous HF yields a peptide construction containing amaximum of three copies of the cyclic disulfide epitope, the lower substitution being attributable tosteric constraints. This immunogen has been successfully used in an experimental vaccination trialagainst foot-and-mouth disease virus.