Cysteine‐Assisted Click‐Chemistry for Proximity‐Driven, Site‐Specific Acetylation of Histones

Post-translational modifications of histones are essential in the regulation chromatin structure and function. Among these modifications, lysine acetylation is one most established. Earlier studies relied on use containing heterogeneous mixtures acetylated at multiple sites. Differentiating individual contribution single events towards thus great relevance. However, it difficult to access homogeneous samples histones, with a acetylation, sufficient quantities for such studies. By engineering histone H3 cysteine proximity interest, we demonstrate that conjugation maleimide-DBCO followed by strain-promoted alkyne-azide cycloaddition reaction results controlled, site-specific manner. The chemical precision offered our click-to-acetylate approach will facilitate study histones.