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Multistep histone synthesis. (a) Total synthesis of H3K56ac using a three-step NCL procedure. (b) Total synthesis of H3K9me3 using Cys-Pro ester fragments, joined by NCL and direct aminolysis in the presence of Ag+ ions. (c) Three-piece semisynthesis to generate H3R42me2a. Initially, two synthetic peptides are joined by NCL. Subsequent activation of a C-terminal acyl hydrazide by oxidation enables a second NCL step to attach a recombinant fragment. pg denotes protecting groups.
