Modular characterization of SARS-CoV-2 nucleocapsid protein domain functions in nucleocapsid-like assembly.

SARS-CoV-2 and its variants, with the Omicron subvariant XBB currently prevailing the global infections, continue to pose threats on public health worldwide. This non-segmented positive-stranded RNA virus encodes the multi-functional nucleocapsid protein (N) that plays key roles in viral infection, replication, genome packaging and budding. N protein consists of two structural domains, NTD and CTD, and three intrinsically disordered regions (IDRs) including the N, the serine/arginine rich motif (SR), and the C.

Palladium-catalyzed disilylation of -halophenylethylenes enabled by 2-pyridone ligand.

A palladium-catalyzed disilylation reaction applicable for a variety of non-, α-, or β-substituted and α,β-disubstituted -halophenylethylenes has been developed. This reaction proceeds with high yields and very low catalyst loadings. The two C-Si bonds of the disilylated products could be well-differentiated chemoselectively in the reaction with various electrophiles.

Emerging roles of O-glycosylation in regulating protein aggregation, phase separation, and functions.

Protein O-glycosylation is widely identified in various proteins involved in diverse biological processes. Recent studies have demonstrated that O-glycosylation plays crucial and multifaceted roles in modulating protein amyloid aggregation and liquid-liquid phase separation (LLPS) under physiological conditions. Dysregulation of these processes is closely associated with human diseases such as neurodegenerative diseases (NDs) and cancers.

Unsymmetric N-heterocyclic carbene ligand enabled nickel-catalysed arylation of bulky primary and secondary amines.

The arylation of sterically hindered amines represents one of the long-standing challenges in synthetic chemistry. Herein, we report a highly efficient Ni-catalysed arylation of sterically hindered primary and secondary amines with aryl chlorides or phenol derivatives enabled by an unsymmetric N-heterocyclic carbene (NHC) ligand. The protocol provides general, efficient, and scalable access to various sterically demanding anilines in excellent yields under mild conditions.

Regio- and enantioselective remote dioxygenation of internal alkenes.

Methods for the enantioselective direct oxygenation of internal alkenes have provided chemists with versatile and powerful toolboxes for the synthesis of optically pure alcohols, one of the most privileged structural motifs. Regioselectivity, however, remains a formidable challenge in the functionalization of internal alkenes. Here we report a palladium-catalysed highly regio- and enantioselective remote 1,n-dioxygenation (n ≥ 4) of internal alkenes with engineered pyridine-oxazoline (Pyox) ligands.

Nickel/biimidazole-catalyzed electrochemical enantioselective reductive cross-coupling of aryl aziridines with aryl iodides.

Here, we report an asymmetric electrochemical organonickel-catalyzed reductive cross-coupling of aryl aziridines with aryl iodides in an undivided cell, affording β-phenethylamines in good to excellent enantioselectivity with broad functional group tolerance. The combination of cyclic voltammetry analysis of the catalyst reduction potential as well as an electrode potential study provides a convenient route for reaction optimization. Overall, the high efficiency of this method is credited to the electroreduction-mediated turnover of the nickel catalyst instead of a metal reductant-mediated turnover.

Target proteins profiling of irreversible kinase inhibitor pelitinib and discovery of degradation of PRDX4 by label free chemoproteomics.

Cell-based methods for profiling the kinase inhibitor selectivity are badly needed, especially for the irreversible kinase inhibitors. Here we reported a chemoproteomics approach for profiling the target proteins of irreversible kinase inhibitor with label free quantitative proteomics by using iodoacetamide alkyne as a chemical probe. In total 41 proteins were identified in high confidence (fold change 3.

Biomarkers of aging.

Aging biomarkers are a combination of biological parameters to (i) assess age-related changes, (ii) track the physiological aging process, and (iii) predict the transition into a pathological status. Although a broad spectrum of aging biomarkers has been developed, their potential uses and limitations remain poorly characterized. An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research: How old are we? Why do we get old? And how can we age slower? This review aims to address this need.

Copper(I)-catalyzed asymmetric alkylation of α-imino-esters.

Asymmetric alkylation of enolates is one of the most direct and important reactions to prepare α-chiral carbonyl compounds. Except for the classical methods that rely on the use of chiral auxiliaries, asymmetric catalysis emerged as a powerful tool, especially asymmetric phase-transfer catalysis. However, in the field of transition metal catalysis, only limited success with asymmetric alkylation of enolates was achieved.

Copper-catalyzed aerobic oxidation of primary alcohols to carboxylic acids.

Here, the first copper-catalyzed aerobic oxidation of primary alcohols to carboxylic acids with TEMPO and KHSO as the co-catalysts has been developed. The reaction exhibits excellent substrate scope and functional group compatibility under mild conditions. Even the very sensitive chiral alcohols, chiral amino alcohols, and alcohol-containing steroid skeletons may be oxidized to afford the corresponding carboxylic acids or lactones without racemization.

Specific pupylation as IDEntity reporter (SPIDER) for the identification of protein-biomolecule interactions.

Protein-biomolecule interactions play pivotal roles in almost all biological processes. For a biomolecule of interest, the identification of the interacting protein(s) is essential. For this need, although many assays are available, highly robust and reliable methods are always desired.

Ultrasonic sample introduction combined with flame assisted thermal ionization: Pretreatment-free direct mass spectrometry analysis for fraction collecting tubes of preparative liquid chromatography.

Ultrasonic sample introduction combined with flame assisted thermal ionization mass spectrometry (USI-FATI-MS) was developed to monitor the fractions of preparative liquid chromatography. Recently, ultrasound-based sample introduction techniques have achieved great advance in the field of high-throughput analysis. However, it is still a challenge to directly apply these existing techniques to the analysis of macro volume samples (mL level).

Differential and substrate-specific inhibition of γ-secretase by the C-terminal region of ApoE2, ApoE3, and ApoE4.

Aberrant low γ-secretase activity is associated with most of the presenilin mutations that underlie familial Alzheimer's disease (fAD). However, the role of γ-secretase in the more prevalent sporadic AD (sAD) remains unaddressed. Here, we report that human apolipoprotein E (ApoE), the most important genetic risk factor of sAD, interacts with γ-secretase and inhibits it with substrate specificity in cell-autonomous manners through its conserved C-terminal region (CT).

A direct observation of up-converted room-temperature phosphorescence in an anti-Kasha dopant-matrix system.

It is common sense that emission maxima of phosphorescence spectra (λ) are longer than those of fluorescence spectra (λ). Here we report a serendipitous finding of up-converted room-temperature phosphorescence (RTP) with λ < λ and phosphorescence lifetime > 0.1 s upon doping benzophenone-containing difluoroboron β-diketonate (BPBF) into phenyl benzoate matrices.

A mass spectrum-oriented computational method for ion mobility-resolved untargeted metabolomics.

Ion mobility (IM) adds a new dimension to liquid chromatography-mass spectrometry-based untargeted metabolomics which significantly enhances coverage, sensitivity, and resolving power for analyzing the metabolome, particularly metabolite isomers. However, the high dimensionality of IM-resolved metabolomics data presents a great challenge to data processing, restricting its widespread applications. Here, we develop a mass spectrum-oriented bottom-up assembly algorithm for IM-resolved metabolomics that utilizes mass spectra to assemble four-dimensional peaks in a reverse order of multidimensional separation.

Enantioselective cyanation of propargylic C-H bonds cooperative photoredox and copper catalysis.

Herein, we report an enantioselective cyanation of propargylic C-H bonds by combining photoredox catalysis with a copper-catalyzed radical relay in which the propargylic radical was generated by an intramolecular 1,5-HAT process. This reaction provides easy access to optically pure propargyl nitrile compounds under mild conditions.

Recent developments in nickel-catalyzed asymmetric cyclization and cycloaddition of carbonyl-alkynes, cyano-alkynes, and enynes.

Alkynes as unsaturated hydrocarbons have long been used for cyclization reactions. Various transition metal-catalyzed cyclizations of alkynes have been reported in the past decades. In this minireview, we mainly summarize the recent asymmetric cyclization of alkynes with other functional groups such as carbonyl-alkynes, cyano-alkynes, and enynes under the catalytic system of nickel and chiral ligands.

Proximity labeling reveals OTUD3 as a DNA-binding deubiquitinase of cGAS.

Cyclic GMP-AMP synthase (cGAS), as the major DNA sensor, initiates DNA-stimulated innate immune responses and is essential for a healthy immune system. Although some regulators of cGAS have been reported, it still remains largely unclear how cGAS is precisely and dynamically regulated and how many potential regulators govern cGAS. Here we carry out proximity labeling of cGAS with TurboID in cells and identify a number of potential cGAS-interacting or -adjacent proteins.

Palladium-catalyzed highly selective -difluoroallylation of propargyl sulfonates with -difluoroallylboron.

A palladium-catalyzed -difluoroallylation of propargyl sulfonates with -difluoroallylboron has been developed. The reaction features synthetic simplicity and high functional group tolerance, affording 3,3-difluoro-skipped 1,5-enynes with high efficiency and regioselectivity. In particular, the resulting products can serve as versatile synthons for diversified transformations, having potential applications in medicinal chemistry.

Selective oxidation of benzylic alcohols synergistic bisphosphonium and cobalt catalysis.

A synergistic photocatalytic system using a bisphosphonium catalyst and a cobalt catalyst has been developed, enabling the selective oxidation of benzylic alcohols under oxidant-free and environmentally benign conditions. High efficiencies have been obtained for a variety of alcohol substrates, and exclusive selectivity for aldehyde products has been achieved across the board. Furthermore, this photocatalytic system proved to be efficient when performed under continuous-flow conditions, even using a simple and easily assembled continuous-flow setup.

Reactivity of vinylidene-π-allyl palladium(II) species.

The reactivity of a new type of organometallic intermediate, vinylidene-π-allyl palladium species, has been demonstrated: the reaction between 4-alken-2-ynyl carbonates and stabilized carbon nucleophiles afforded functionalized 1,2,3,-butatriene compounds in moderate to high yields and excellent regioselectivities.