An adenine base editor variant expands context compatibility.

Adenine base editors (ABEs) are precise gene-editing agents that convert A:T pairs into G:C through a deoxyinosine intermediate. Existing ABEs function most effectively when the target A is in a TA context. Here we evolve the Escherichia coli transfer RNA-specific adenosine deaminase (TadA) to generate TadA8r, which extends potent deoxyadenosine deamination to RA (R = A or G) and is faster in processing GA than TadA8.

Transcriptome-wide profiling and quantification of N-methyladenosine by enzyme-assisted adenosine deamination.

N-methyladenosine (mA), the most abundant internal messenger RNA modification in higher eukaryotes, serves myriad roles in regulating cellular processes. Functional dissection of mA is, however, hampered in part by the lack of high-resolution and quantitative detection methods. Here we present evolved TadA-assisted N-methyladenosine sequencing (eTAM-seq), an enzyme-assisted sequencing technology that detects and quantifies mA by global adenosine deamination.

Controllable catalytic difluorocarbene transfer enables access to diversified fluoroalkylated arenes.

Difluorocarbene has important applications in pharmaceuticals, agrochemicals and materials, but all these applications proceed using just a few types of reaction by taking advantage of its intrinsic electrophilicity. Here, we report a palladium-catalysed strategy that confers the formed palladium difluorocarbene (Pd=CF) species with both nucleophilicity and electrophilicity by switching the valence state of the palladium centre (Pd(0) and Pd(II), respectively). Controllable catalytic difluorocarbene transfer occurs between readily available arylboronic acids and the difluorocarbene precursor diethyl bromodifluoromethylphosphonate (BrCFPO(OEt)).

Transition-Metal (Cu, Pd, Ni)-Catalyzed Difluoroalkylation via Cross-Coupling with Difluoroalkyl Halides.

Difluoroalkylated compounds play a remarkably important role in life and materials sciences because of the unique characteristics of the difluoromethylene (CF) group. In particular, precise introduction of a CF group at the benzylic position can dramatically improve the biological properties of the corresponding molecules. As a consequence, difluoroalkylation of aromatic compounds has become a powerful strategy in modulating the bioactivities of organic molecules.

Bulky Diamine Ligand Promotes Cross-Coupling of Difluoroalkyl Bromides by Iron Catalysis.

Although iron-catalyzed cross-coupling of Grignard reagents with alkyl halides has been well established, the adoption of the reaction for fluoroalkylations has not been reported because traditional catalytic systems often lead to defluorination reactions. Described herein is the investigation of an iron-catalyzed cross-coupling between arylmagnesium bromides and difluoroalkyl bromides with modified N,N,N',N'-tetramethyl-ethane-1,2-diamine (TMEDA) as a ligand. The use of this bulky diamine, in which a butylene is substituted at one carbon atom of the ethylene backbone in TMEDA, enables the iron-catalyzed difluoroalkylation under mild reaction conditions with a wide range of difluoroalkyl bromides, including vulnerable bromodifluoromethane, thus providing a general and cost-efficient route for applications in medicinal chemistry.

Copper-Catalyzed Highly Stereoselective Trifluoromethylation and Difluoroalkylation of Secondary Propargyl Sulfonates.

It is challenging to stereoselectively introduce a trifluoromethyl group (CF ) into organic molecules. To date, only limited strategies involving direct asymmetric trifluoromethylation have been reported. Herein, we describe a new strategy for direct asymmetric trifluoromethylation through the copper-catalyzed stereospecific trifluoromethylation of optically active secondary propargyl sulfonates.

Nickel-Catalyzed Difluoroalkylation of (Hetero)Arylborons with Unactivated 1-Bromo-1,1-difluoroalkanes.

A nickel-catalyzed cross-coupling between (hetero)arylborons and unactivated 1-bromo-1,1-difluoroalkanes has been developed. The use of two ligands (a bidentate bipyridine-based ligand, 4,4'-ditBu-bpy, and a monodentate pyridine-based ligand, DMAP) offers a highly efficient nickel-based catalytic system to prepare difluoroalkylated arenes which have important applications in medicinal chemistry.

TMPyP4-regulated cell proliferation and apoptosis through the Wnt/β-catenin signaling pathway in SW480 cells.

Background: The aim of this study was to investigate the potential effects of the 5, 10, 15, 20-tetrakis (1-methylpyridinium-4-yl) porphyrin (TMPyP4) on the proliferation and apoptosis of SW480 cells and the underlying mechanisms by which TMPyP4 exerted its actions.

Methods: After treated with different doses of TMPyP4, cell viability was determined by MTT method, the apoptosis was observed by flow cytometry (FCM) and the expression of Wnt, GSK-3β, β-catenin and cyclinD1 was measured by RT-PCR and Western blot analysis.

Results: The analysis revealed that TMPyP4 potently suppressed cell viability and induced the apoptosis of SW480 cells in a dose-dependent manner.

Facile Access to Fluoromethylated Arenes by Nickel-Catalyzed Cross-Coupling between Arylboronic Acids and Fluoromethyl Bromide.

The nickel-catalyzed fluoromethylation of arylboronic acids was achieved with the industrial raw material fluoromethyl bromide (CH2 FBr) as the coupling partner. The reaction proceeded under mild reaction conditions with high efficiency; it features the use of a low-cost nickel catalyst, synthetic simplicity, and excellent functional-group compatibility, and provides facile access to fluoromethylated biologically relevant molecules. Preliminary mechanistic studies showed that a single-electron-transfer (SET) pathway is involved in the catalytic cycle.

Heteroaryldifluoromethylation of organoborons catalyzed by palladium: facile access to aryl(heteroaryl)difluoromethanes.

A first example of Pd-catalyzed heteroaryldifluoromethylation of organoborons with bromodifluoromethylated heteroarenes has been described. The use of phosphine ligand PAd2(n-Bu)·HI is critical for the reaction efficiency. With use of this ligand, a wide range of aryl(heteroaryl)difluoromethanes were obtained with high efficiency.

Nickel-catalyzed cross-coupling of functionalized difluoromethyl bromides and chlorides with aryl boronic acids: a general method for difluoroalkylated arenes.

Transition-metal-catalyzed difluoroalkylation of aromatics remains challenging despite the importance of difluoroalkylated arenes in medicinal chemistry. Herein, the first successful example of nickel-catalyzed difluoroalkylation of aryl boronic acids is described. The reaction allows access to a variety of functionalized difluoromethyl bromides and chlorides, and paves the way to highly cost-efficient synthesis of a wide range of difluoroalkylated arenes.

Direct olefination of fluorinated benzothiadiazoles: a new entry to optoelectronic materials.

Fluorinated olefin-containing benzothiadiazoles have important applications in optoelectronic materials. Herein, we reported the direct olefination of fluorinated benzothiadiazoles, as catalyzed by palladium. The reaction proceeds under mild reaction conditions and shows high functional-group compatibility.

Palladium-catalyzed difluoroalkylation of aryl boronic acids: a new method for the synthesis of aryldifluoromethylated phosphonates and carboxylic acid derivatives.

The palladium-catalyzed difluoroalkylation of aryl boronic acids with bromodifluoromethylphosphonate, bromodifluoroacetate, and further derivatives has been developed. This method provides a facile and useful access to a series of functionalized difluoromethylated arenes (ArCF2 PO(OEt)2 , ArCF2 CO2 Et, and ArCF2 CONR(1) R(2) ) that have important applications in drug discovery and development. Preliminary mechanistic studies reveal that a single electron transfer (SET) pathway may be involved in the catalytic cycle.

[Distribution of Chinese medicine syndrome patterns and its laws in patients with polycystic ovarian syndrome].

Objective: To study the distribution laws of the Chinese medicine syndrome patterns and its correlated symptoms in patients with polycystic ovarian syndrome (PCOS), and the possible correlation between Chinese medicine syndrome patterns and PCOS associated parameters, thus to provide a guidance for selecting proper indices in curative effectiveness assessment.

Methods: Using clinical epidemiological methods and mathematical statistics, the Chinese medicine syndrome patterns were studied in 228 PCOS patients. The distribution features of Chinese medicine syndrome patterns were summarized.