Figure 4.
Multistep semisynthesis of histone H3 methylated at Arg-42. A three-piece sequential ligation scheme was used to assemble H3 containing a dimethyl arginine at position 42. Use of a peptide hydrazide in the central fragment allowed the synthesis to proceed in an N-to-C direction. Free radical desulfurization, as the final step, yielded the desired posttranslational modification–containing protein. Yellow indicates a building block of synthetic origin in the final construct, whereas blue indicates a recombinantly prepared fragment in the final construct. Abbreviations: Boc, butyloxycarbonyl; Fmoc, fluorenylmethyloxycarbonyl; MPAA, mercaptophenylacetic acid; NCL, native chemical ligation reaction; SPPS, solid-phase peptide synthesis.
