Lipidation of Cysteine or Cysteine‐Containing Peptides Using the Thiol‐Ene Reaction (CLipPA)

Abstract The efficient synthesis of N α ‐protected S ‐palmitoylated cysteine building blocks using thiol‐ene coupling is described. These building blocks were incorporated into a resin‐bound peptide under racemisation‐suppressing conditions, and the degree of racemisation during the coupling process was assessed. The direct conjugation of vinyl palmitate with the sulfhydryl side‐chain of a cysteine residue on a semiprotected peptide was also studied. The reaction gave both mono‐ and bispalmitoylated cysteine residues in varying proportions, depending on the reaction conditions adopted.