Synthesis of N alpha-Fmoc protected derivatives of S-(2,3-dihydroxypropyl)-cysteine and their application in peptide synthesis.

Acylated derivatives of S-(2,3-dihydroxypropyl)-cysteine (S-glycerylcysteine) form the N-terminus of structural and functional proteins of bacterial origin. Synthetic lipopeptides containing tripalmitoyl-S-glycerylcysteine are derived from bacterial lipoprotein and constitute potent immunoadjuvants activating both B-lymphocytes and macrophages. There is increasingly interest in conjugates consisting of tripalmitoyl-S-glycerylcysteine linked to appropriate viral and bacterial antigens, because of their capability of inducing antigen specific antibodies and T-helper and T-killer cell specific immune responses. A new convenient synthetic pathway for the preparation of these tripalmitoyl-S-glycerylcysteinyl peptides is described. The use of N alpha-Fmoc-protected S-(2,3-dihydroxypropyl)-cysteine and its O,O'-bis acylated derivatives for the synthesis of triacyl-S-glycerylcysteinyl, O,O'-bis-acyl-S-glycerylcysteinyl and S-glycerylcysteinyl peptides of high diastereomeric purity by solid phase peptide synthesis or synthesis in solution is demonstrated.