Synthesis of novel immunologically active tripalmitoyl-S-glycerylcysteinyl lipopeptides as useful intermediates for immunogen preparations

The synthesis and characterization of lipopeptides consisting of the lipoamino acid N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-[R]-cysteine (Pam,Cys-OH) and different peptide segments and/or spacer molecules is described. Pam,Cys-peptides, which are derived from the immunologically active TV-terminus of bacterial lipoprotein, were obtained either by solution or solid phase peptide synthesis. In particular, the amphiphilic and water-soluble lipohexapeptides Pam₃Cys-Ser-(Lys)₄ and Pam₃Cys-Ser-(Glu)₄ proved to be potent macrophage and B-cell activators and non-toxic, non-pyrogenic immune adjuvants in combination with or covalently linked to antigens and haptens.