Synthesis of Peptide-Based Vaccines
Lipopeptides are potent and non-toxic adjuvants. Peptides by themselves are poor immunogens, even when incorporated in liposomes. For effective interaction with both the innate and adaptive immune responses, peptides must be conjugated with one of several known lipid moieties.
Tri- or dipalmitoyl-S-glyceryl-Cys-Ser-Ser, based on a bacterial lipoprotein, was found to be an effective adjuvant  that was later replaced by the more readily synthesized dipalmitoyl-Lys-Ser-Ser . The purification of lipopeptides remains a problem, however, due to low aqueous solubility and the loss of resolution using traditional HPLC technology. Moreover, difficulties in their analysis hinder the use of such peptide-based vaccines in human clinical experiments. Purification of the unprotected peptides prior to conjugation of whatever lipid modification being used is highly desirable. Methods now available rely on exploitation of Cys residues for conjugation. Maleimide-based conjugation is...
KeywordsPoor Immunogen HPLC Purity Native Chemical Ligation Bacterial Lipoprotein Kaiser Test