A chemical catalyst enabling histone acylation with endogenous acyl-CoA.

Life emerges from a network of biomolecules and chemical reactions catalyzed by enzymes. As enzyme abnormalities are often connected to various diseases, a chemical catalyst promoting physiologically important intracellular reactions in place of malfunctional endogenous enzymes would have great utility in understanding and treating diseases. However, research into such small-molecule chemical enzyme surrogates remains limited, due to difficulties in developing a reactive catalyst capable of activating inert cellular metabolites present at low concentrations.

Synthetic hyperacetylation of nucleosomal histones.

We report combinations of a DMAP-based catalyst and phenyl acetate with optimal electron density as a new chemical system for high-yield, selective synthetic acetylation of histone lysine residues. The utility of this chemical system as a unique biologic tool is demonstrated by applying it to sperm chromatin.

Leading approaches in synthetic epigenetics for novel therapeutic strategies.

In recent years, our knowledge of the epigenetic functions regulated by post-translational modifications (PTMs) of histones, and their role in various diseases, has expanded rapidly, opening the way to novel therapeutic strategies that treat epigenetic abnormalities. Many of the current approaches have been focusing on the chemical inhibition of histone-modifying enzymes to modulate histone PTM states for attaining therapeutic effects. However, recent developments in chemistry and molecular biology have contributed to the emergence of new methods that introduce histone PTMs entirely through artificial means, without reliance on endogenous enzymes.

Supramolecular Ligands for Histone Tails by Employing a Multivalent Display of Trisulfonated Calix[4]arenes.

Post-translational modification of histone tails plays critical roles in gene regulation. Thus, molecules recognizing histone tails and controlling their epigenetic modification are desirable as biochemical tools to elucidate regulatory mechanisms. There are, however, only a few synthetic ligands that bind to histone tails with substantial affinity.