Chemical synthesis of palmitoylated histone H4

Abstract

Palmitoylation is one of the post-translational modifications of proteins. Recently, palmitoyl modification was found in histone H4, one of the components of the nucleosome core. To analyze this unusual modification in the nuclear protein, we chemically synthesized Ser47-palmitoylated histone H4. The entire sequence of H4 was divided into three segments and each was prepared by Fmoc-solid-phase peptide synthesis (SPPS). The palmitoyl group was introduced as a preformed palmitoyl Ser during SPPS or introduced at the end of SPPS by selective deprotection of the hydroxy group of Ser47, followed by palmitoylation. After three segments were condensed in one-pot by the thioester method, the desired Ser47-palmitoylated H4 was obtained.