Total synthesis and structural characterization of caveolin‐1

Caveolin-1, which is an essential protein for caveola formation, was chemically synthesized. It is composed of 177 amino acid residues, triply palmitoylated at the C-terminus region and supposed to be inserted into the lipid bilayer forming a V-shaped structure in the middle of the polypeptide chain. The entire sequence was divided into 5 peptide segments and each of them was synthesized by the solid-phase method. To improve the solubility of the C-terminal region, the O-acyl isopeptide structures were incorporated. After the ligation by the thioester method and the introduction of the palmitoyl groups, all the protecting groups were removed and the isopeptide structures were converted to the native peptide bond. Finally, the obtained polypeptide was successfully inserted into the bicelle, thus showing the success of the synthesis.