Histones: At the Crossroads of Peptide and Protein Chemistry

Featuring the nucleosome surface as a therapeutic target

“…To investigate the function of histones and peptides derived from histone tails, great work has been done by synthetic biologists in the past decade [21]. Structural studies of large complexes have been resolved by cryo-EM, such as the 30-nm fiber structure published recently [14].…”

“…Recently, many synthetic peptides derived from the histone tail and its post-translational modification were systematically reviewed [21], focusing on their contributions to peptide chemistry, chromatin biology, and cellular signaling. We wonder whether any of these peptides, with high affinity for the acidic patch, have been directly tested in cellular and animal models and, if so, what would be their effects on chromatin structure, global gene expression, cell proliferation, viability, and, for example, various types of cancer.…”

Analytical strategies used to identify the readers of histone modifications: A review

“…Thus, the synthesized nucleosome provides a "real" chromatin as a analytical probe to capture binders of HPTMs. It is reasonable to assume that the necleosome assay will be a powerful analytical tool for the identification of HPTM binders or for other epigenetic research when combined with quantitative MS techniques [96]. Recent advancements have further expanded the catalog of HPTMs [97], including those newly identified modifications such as lysine propionylation, butyrylation [98,99], crotonylation [100], succinylation [101] and 2-hydroxyisobutyrylation [102].…”

Emerging Chemistry Strategies for Engineering Native Chromatin

“…The availability of multiple protein engineering strategies for introducing PTMs means that synthetic routes can now be found for the majority of modified histone targets one might wish to study 24 —these routes can, if necessary, involve the integrated use of these methods. 29,30 Thus, as we write this piece, many dozens of modified histones have been generated using chemistry-driven methods.…”