Total chemical synthesis of tyrosine iodinated histone through four-segment sequential native chemical ligation

Histone post-translational modifications play critical roles in dynamic regulation of chromatin structure. For instance, histone iodination has been confirmed to directly influence the stability of the histone core. However, it remains difficult for the construction of atom-customized iodinated histones for biochemical and biophysical studies. Here we report a practical strategy for the total chemical synthesis of homogenous histone H2B-Y81-iodination through the sequential ligation of four segments based on peptide hydrazides. The synthesized Y81-iodinatied H2B can be used for the construction of iodinated nucleosomes. Our results showed that iodinated histones synthesized by utilizing this strategy can provide multi-milligram-scale protein for biochemical studies.