A Method for the Generation of Pam2Cys-Based Lipopeptide Mimics via CuAAC Click Chemistry

Abstract

The immunostimulatory activity of naturally occurring lipopeptides as bacterial cell wall components arises due to the presence of certain lipid motifs. S- [2,3-bis(palmitoyloxy)propyl]cysteine (Pam 2 Cys) is a lipid motif known to successfully reproduce this immunostimulatory activity when incorporated into synthetic peptides. Herein we report the synthesis of a Pam 2 Cys analogue designed to facilitate the fully convergent, efficient generation of lipopeptide mimics using click chemistry to effect its ligation to suitably functionalized peptides. The incorporation of this Pam 2 Cys mimic into peptides prepared by SPPS is also demonstrated.