Simultaneous Lipidation of a Characterized Peptide Mixture by Chemoselective Ligation
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- 作者：Line Bourel-Bonnet ; Dominique Bonnet ; Fré ; dé ; ric Malingue ; Hé ; lè ; ne Gras-Masse ; and Oleg Melnyk
- 刊名：Bioconjugate Chemistry
- 出版年：2003
- 出版时间：March 2003
- 年：2003
- 卷：14
- 期：2
- 页码：494 - 499
- 全文大小：116K
- 年卷期：v.14,no.2(March 2003)
- ISSN：1520-4812
文摘
The modification of a peptide antigen by a fatty acid such as palmitic acid is now recognized as amean to induce cellular responses. Mixtures of lipopeptides, obtained by combining individuallysynthesized compounds, were shown to be promising synthetic vaccine candidates. Usually, inlipopeptide synthesis, the fatty acyl moiety is introduced on the crude peptide chain using solid-phasemethods. The separation of the target compound from impurities by RP-HPLC is often complicatedby the amphiphilic properties of lipopeptides and results in low overall yields. To overcome thedifficulties associated with lipopeptide synthesis and mixture preparation, we have developed a methodwhere the fatty acyl moiety is site-specifically and collectively introduced in solution onto a mixtureof individually prepurified peptides. The lipidation is based on the quasistoichiometric and high-yielding ligation of a glyoxylyl lipid with hydrazinoacetyl peptides. The hydrazone constructs wereprepared in a salt-free medium and could be isolated by direct lyophilization of the reaction mixture.This process is compatible with cysteinyl peptides, and no aggregation nor degradation could beobserved.