Chemical Catalyst‐Promoted Regioselective Histone Acylation

Histone post-translational modifications play pivotal roles in epigenome, which regulates gene expression. Dysregulation of these modifications can lead to diseases, such as cancer. Therefore, epigenome editing methods will be biologic tools and novel therapeutics. Chemical catalyst-promoted histone modifications are especially promising because genetic manipulations are not necessary. A supramolecular approach is useful for developing chemical catalysts surrogating as enzymes and promoting selective modifications of histones in a biologic environment. We developed LANA-DSH catalyst 6 , which promoted histone- and regio (H2BK120)-selective acylation under physiological conditions in test tubes. Furthermore, PEG-LANA-DSSMe catalysts 14 – 16 promoted H2BK120 acetylation in living cells containing numerous off-target molecules. Similar to protecting group strategies used in organic synthesis, the catalyst-promoted H2BK120 acetylation suppressed physiological H2BK120 ubiquitination, which plays an important role in the development of certain types of cancer. Thus, our supramolecular catalyst system might be a seed for a unique anticancer strategy through promoting synthetic epigenetics.