A technique for the synthesis of highly-pure, mono-epitopic, multi-valent lipid core peptide vaccines

The synthesis of lipid core peptide (LCP) vaccines using stepwise solid-phase peptide synthesis commonly results in products which are difficult to purify to homogeneity. A new technique for synthesizing highly-pure, mono-epitopic, multi-valent LCP-systems using native chemical ligation is presented. Various conditions were assessed for ligating four copies of a thioester-modified 88/30 serotype group A streptococcal peptide antigen onto an LCP-system featuring four cysteine residues. Overall, the vaccine was synthesized in high purity (>99%), and high yield (90%) when the ligation reaction was performed in the presence of 1% sodium dodecyl sulfate and at elevated temperatures (37 degrees C). (C) 2007 Elsevier Ltd. All rights reserved