Hybrid phase ligation for efficient synthesis of histone proteins

We introduce a hybrid solid-solution phase ligation approach that combines the efficiency of solid phase ligation with solution phase ligation in the total synthesis of modified histone proteins. A two linker strategy allows analysis throughout work on the solid phase and maximizes yields through cleavage at an external Rink, while an internal HMBA linker allows the native carboxyl terminus for any protein sequence. We demonstrate this approach for two histone proteins: triple-acetylated H4-K5ac, K12ac, K91ac and CENP-A-K124ac.