Synthesis of a B-Lymphocyte Activating α-Methylserine Containing Lipopentapeptide

The lipopentapeptide S-[2,3-bis(palmitoyloxy)-[2-R,S]-propyl]-N-palmitoyl-[R]-cysteinyl-[ R|- α-methylseryI-[R]-α-methylseryl-[S]-asparaginyl-[S]-alanine (Pam3Cys-α-MeSer-α-MeSer-Asn -Ala) has been synthesized as an analogue of the immunoadjuv- ant Pam3Cys-Ser-Ser-Asn -Ala (TPP) via fragment condensations. The two [R]-α-methylserine residues were introduced instead of [L]-serine in order to obtain a mitogenic lipopeptide resistant against proteases. As the parent lipopeptide TPP the analytically pure analogue with McSer was found to induce enhanced cell proliferation of spleen lymphocytes.