A Live-Cell Epigenome Manipulation by Photo-Stimuli-Responsive Histone Methyltransferase Inhibitor.

Post-translational modifications on the histone H3 tail regulate chromatin structure, impact epigenetics, and hence the gene expressions. Current chemical modulation tools, such as unnatural amino acid incorporation, protein splicing, and sortase-based editing, have allowed for the modification of histones with various PTMs in cellular contexts, but are not applicable for editing native chromatin. The use of small organic molecules to manipulate histone-modifying enzymes alters endogenous histone PTMs but lacks precise temporal and spatial control. To date, there has been no achievement in modulating histone methylation in living cells with spatiotemporal resolution. In this study, a new method is presented for temporally manipulating histone dimethylation H3K9me2 using a photo-responsive inhibitor that specifically targets the methyltransferase G9a on demand. The photo-caged molecule is stable under physiological conditions and cellular environments, but rapidly activated upon exposure to light, releasing the bioactive component that can immediately inhibit the catalytic ability of the G9a in vitro. Besides, this masked compound could also efficiently reactivate the inhibition of methyltransferase activity in living cells, subsequently suppress H3K9me2, a mark that regulates various chromatin functions. Therefore, the chemical system will be a valuable tool for manipulating the epigenome for therapeutic purposes and furthering the understanding of epigenetic mechanisms.

Flavin mononucleotide regulated photochemical isomerization and degradation of zeatin.

cis-Zeatin (cZ), a cytokinin often overlooked compared to trans-zeatin (tZ), can now be controlled in live cells and plants through a new biocompatible reaction. Using flavin photosensitizers, cZ can be isomerized to tZ or degraded, depending on the presence of a reducing reagent. This breakthrough offers a novel approach for regulating plant growth through chemical molecules.

Recent Advances towards the Reversible Chemical Modification of Proteins.

Proteins are intriguing biomacromolecules for all living systems, not only as essential building blocks of organisms, but also as participants in almost every aspect of cellular activity such as metabolism and gene transcription/expression. Developing chemical biology tools that are capable of labeling/modifying proteins is a powerful method for decoding their detailed structures and functions. However, most current approaches heavily rely on the installation of permanent tags or genetic engineering of unnatural amino acids. There has been slow development in reversible chemical labeling using small organic probes and bioorthogonal transformations to construct site-selectively modified proteins and conditionally restore their activities or structures. This review summarizes recent advances in the field of chemical regulation of proteins with reversible transformations towards distinct motifs, including amino acid residues, amide backbones and native post-translational lysine. Finally, current challenges and future perspectives are discussed.

Four-Component Radical Dual Difunctionalization (RDD) of Two Different Alkenes with Aldehydes and tert-Butyl Hydroperoxide (TBHP): An Easy Access to ß,δ-Functionalized Ketones.

A convenient Fe-catalyzed four-component radical dual difunctionalization and ordered assembly of two alkenes with aromatic/aliphatic aldehydes and TBHP to provide chain elongated ß,δ-functionalized ketones via a one-pot procedure has been developed. Aldehydes were homolytically cleavaged to produce acyl radicals and subsequently allowed for the successive construction of C(sp2)-C(sp3), C(sp3)-C(sp3), and C(sp3)-O bonds via dual radical insertions and radical-radical coupling, following the intrinsic nucleo/electrophilic reactivity of both the radicals and alkenes.

Correction: Fe-Catalyzed three-component carboazidation of alkenes with alkanes and trimethylsilyl azide.

Correction for 'Fe-Catalyzed three-component carboazidation of alkenes with alkanes and trimethylsilyl azide' by Wei-Yu Li et al., Chem. Commun., 2018, DOI: .

Fe-Catalyzed three-component carboazidation of alkenes with alkanes and trimethylsilyl azide.

Reported herein is a novel iron-catalyzed, DTBP-mediated carboazidation of alkenes using cycloalkanes, CH2Cl2, CHCl3 and CCl4 as alkylating reagents to generate electrophilic or nucleophilic alkyl radicals. Mechanistic studies suggested that the reaction proceeded via the addition of alkyl radicals to alkenes followed by an iron-mediated ligand transfer process. The reaction is unique as it is applicable not only to diversely functionalized electron rich alkenes, but also to electron-poor olefins to provide chain extended azides and γ-azido chloroalkanes in good to high yields.