An Improved Method for the Synthesis of Lipopeptide TLR2-Agonists Using Click Chemistry

S -[2,3-Bis(palmitoyloxy)propyl]cysteine (Pam 2 Cys) is a synthetic lipid motif known to act as a TLR2 agonist when incorporated into peptide vaccines. Herein, we report the synthesis of Pam 2 Cys-containing, propargyl-functionalised ‘clickable’ building blocks and their conjugation with azide-functionalised antigenic peptides using click chemistry. This method facilitates the fully convergent preparation of self-adjuvanting lipopeptides for use as vaccines.