CHEMICAL PAPERS
·
2014
·Vol. 68
·期 10
·1408-1414
·
IF 1.193
Cao Meng,Hu Hua-You,Zhao Hu-Cheng,Zhang Xi-Quan,Gu Hong-Mei,Yang Ling,Cai Jin,Wang Peng,Hu Bing,Ji Min
In the current study a facile synthetic route for preparing antineoplastic drug GDC-0449 is investigated. Starting with pyridine-1-oxide and 1-iodo-3-nitrobenzene, the intermediate product 2-(2-chloro-5-nitrophenyl) pyridine was prepared by cross-coupling, deoxidation and halogenation. The final compound was then synthesised by reduction of the nitro group followed by amidation. This synthetic route avoids the use of unstable organometallic or organic boride compounds; it employs relatively inexpensive and bench-stable reagents, involves readily controllable reaction conditions, and achieves a relatively high yield.
研究领域:
药物化学
·
有机合成
·
肿瘤学
✓ 已验证
DOI
高影响因子
CHEMBIOCHEM
·
2017
·Vol. 19
·期 5
·521-526
·
IF 2.847
Zheng Zhou,Min Li,Jian-He Xu,Zhi-Jun Zhang
Graphical Reduced to clear : The nitrile reductase from Pectobacterium carotovorum is able to catalyze the reduction of nitriles to primary amines with the consumption of two molecules of NADPH. A single mutation at the entrance of the substrate channel increases both the activity and stability of the nitrile reductase. Nitrile reductases are considered to be promising and environmentally benign nitrile-reducing biocatalysts to replace traditional metal catalysts. Unfortunately, the catalytic efficiencies of the nitrile reductases reported so far are very low. To date, all attempts to increase the catalytic activity of nitrile reductases by protein engineering have failed. In this work, we successfully increased the specific activity of a nitrile reductase from Pectobacterium carotovorum from 354 to 526 U g prot −1 by engineering the substrate binding pocket; moreover, the thermostability was also improved (≈2-fold), showing half-lives of 140 and 32 h at 30 and 40 °C, respectively. In the bioreduction of 2-amino-5-cyanopyrrolo[2,3- d ]pyrimidin-4-one (preQ 0 ) to 2-amino-5-aminomethylpyrrolo[2,3- d ]pyrimidin-4-one (preQ 1 ), the variant was advantageous over the wild-type enzyme with a higher reaction rate and complete conversion of the substrate within a shorter period. Homology modeling and docking analysis revealed some possible origins of the increased activity and stability. These results establish a solid basis for future engineering of nitrile reductases to increase the catalytic efficiency further, which is a prerequisite for applying these novel biocatalysts in synthetic chemistry.
研究领域:
生物化学
·
合成生物学
✓ 已验证
DOI
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Xianbao Sun,Lingling Xu,Hai-Dong Xu,Limin Xie,Rui Wang,Zhimou Yang,Wenjun Zhan,Shurong Shen,Gaolin Liang
Current molecular photoacoustic (PA) probes are designed with either stimulus-turned “on” or assembly-enhanced signals to trace biological analytes/events. PA probes based on the nature-derived click reaction between 2-cyano-6-aminobenzothiazole (CBT) and cysteine (Cys) (i.e., CBT-Cys click reaction) possess both “turn-on” and “enhanced” PA signals; and thus, should have higher sensitivity. Nevertheless, such PA probes, particularly those for sensitive imaging of tumor hypoxia, remain scarce. Herein, a PA probe NI-Cys(StBu)-Dap(IR780)-CBT (NI-C-CBT) is rationally designed, which after being internalized by hypoxic tumor cells, is cleaved by nitroreductase under the reduction condition to yield cyclic dimer C-CBT-Dimer to turn the PA signal “ON” and subsequently assembled into nanoparticles C-CBT-NPs with additionally enhanced PA signal (“Enhanced”). NI-C-CBT exhibits 1.7-fold “ON” and 3.2-fold overall “Enhanced” PA signals in vitro. Moreover, it provides 1.9-fold and 2.8-fold overall enhanced PA signals for tumor hypoxia imaging in HeLa cells and HeLa tumor-bearing mice, respectively. This strategy is expected to be widely applied to design more “smart” PA probes for sensitive imaging of important biological events in vivo in near future.
研究领域:
生物医学工程
·
分子影像学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
ANALYST
·
2018
·Vol. 144
·期 1
·284-289
·
IF 3.864
Lei Zhang,Xue Shan,Leilei Guo,Jikang Zhang,Junliang Ge,Qing Jiang,Xinghai Ning
Nitroreductase activities are positively associated with the hypoxic level of tumors, making it an attractive target for tumor detection. Herein, we have developed a 2,5-bis(methylsulfinyl)-1,4-diaminobenzene based probe (BBP), which is a nitroreductase (NTR) responsive fluorescent probe and can rapidly detect NTRs with high sensitivity and specificity. The BBP showed not only a selective response to NTRs over other biological reductants, but also high sensitivity to NTRs and could detect as low as 20 ng mL−1 NTRs. Furthermore, the BBP responded rapidly to NTRs in as fast as 10 minutes, enabling real-time monitoring of the production levels of NTRs. Most importantly, the BBP could identify NTR activities in 2D cell monolayers, 3D tumor spheroids, and even solid tumors in mice. Particularly, the BBP could monitor the early tumor formation and treatment response via measuring NTR activities. Overall, the BBP appears to be an ideal imaging probe for the detection of solid tumors, and possesses great potential in a broad range of diagnostic and therapeutic applications in the clinic.
研究领域:
肿瘤学
·
分子影像学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry A
·
2020
·Vol. 8
·期 9
·4807-4815
·
IF 11.301
Ying Gu,Aiping Wu,Lei Wang,Dongxu Wang,Haijing Yan,Peng Yu,Ying Xie,Chungui Tian,Fanfei Sun,Honggang Fu
Single-atom catalysts (SACs) have been promising in various catalytic fields, but the controllable synthesis of SACs with high stability remains challenging. Here, we show a robust strategy toward the fabrication of highly efficient and stable SACs based on the “competitive occupancy” of two metal (M) species on graphene oxide (GO). The abundant M1 (Ti) species predominantly occupy more groups of GO, thereby leaving a tiny number of groups in the gaps of the M1 species to combine with M2 (Co2+, etc.) species. Consequently, this guarantees the formation of Co–N4 SACs embedded in 2D TiN/rGO sheets during nitridation. Further, TiN can act as a “spacer” to prevent Co–N4 from aggregation, thereby improving catalyst stability. Co–N4/TiN–rGO exhibits outstanding catalytic performance for the fast conversion of highly concentrated aromatic nitro compounds (∼0.3–2 mM) into amino compounds and excellent recyclability, which is the best among reported catalysts. In contrast, TiN/rGO has no obvious activity, and Co4N–rGO prepared without Ti competition shows poor activity and stability, which indicates the vital role of Co–N4 and TiN for obtaining the remarkable catalytic ability of Co–N4/TiN–rGO. The reaction mechanism is also proposed based on theoretical calculations. The strategy can be used to design Ni (Fe, Cr, Cu)-based SACs.
研究领域:
材料科学
·
催化化学
✓ 已验证
DOI
高影响因子
Analytical Methods
·
2021
·Vol. 13
·期 19
·2223-2228
·
IF 2.896
Bo-Wen Liu,Peng-Cheng Huang,Fang-Ying Wu
A novel and efficient light-controlled colorimetric assay for the quantification and detection of nitroreductase (NTR) was constructed based on p-aminophenol (pAP)-catalyzed and nicotinamide adenine dinucleotide (NADH)-mediated generation of AgNPs. Due to the hydrolysis of p-nitrophenol by NTR in the presence of NADH, the hydrolysis product can be used as a catalyst to catalyze the reduction of Ag+ by NADH under the light. As the concentration of NTR increases, the value of absorbance at ca. 400 nm (A400) decreases and the color of the solution turns from brown to bright yellow. A linear correlation was obtained between A400 and the NTR concentration in the range from 1–50 μg mL−1 and the limit of detection (LOD) is 0.27 μg mL−1. The detection system does not respond to other common biological molecules due to the specificity of enzymes and the effect of the nitroreductase inhibitor on the NTR activity was also tested. Finally, we applied the assay to determine NTR in human serum samples by spiking different concentrations of NTR with a recovery of 85.2%–92.5%.
研究领域:
生物化学
·
医学检测
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
PLANT CELL AND ENVIRONMENT
·
2021
·Vol. 44
·期 9
·3173-3183
·
IF 7.228
Kunlong Su,Zhenying Wu,Yuchen Liu,Shanshan Jiang,Dongmei Ma,Yan Wang,Chunxiang Fu
Dinitrotoluene (DNT) has been extensively used in manufacturing munitions, polyurethane foams and other important chemical products. However, it is highly toxic and mutagenic to most organisms. Here, we synthesized a codon-optimized bacterial nitroreductase gene, NfsI, for plant expression. The kinetic analysis indicates that the recombinant NfsI can detoxify both 2,4-DNT and its sulfonate (DNTS), while it has a 97.6-fold higher catalytic efficiency for 2,4-DNT than DNTS. Furthermore, we overexpressed NfsI in switchgrass ( Panicum virgatum L.), which is a multiple-purpose crop used for fodder and biofuel production as well as phytoremediation. The 2,4-DNT treatment inhibited root elongation of wild-type switchgrass plants and promoted reactive oxygen species (ROS) accumulation in roots. In contrast, overexpression of NfsI in switchgrass significantly alleviated 2,4-DNT-induced root growth inhibition and ROS overproduction. Thus, the NfsI overexpressing transgenic switchgrass plant removed 94.1% 2,4-DNT after 6 days, whose efficiency was 1.7-fold higher than control plants. Moreover, the comparative transcriptome analysis suggests that 22.9% of differentially expressed genes induced by 2,4-DNT may participate in NfsI-mediated 2,4-DNT detoxification in switchgrass. Our work sheds light on the function of NfsI during DNT phytoremediation for the first time, revealing the application potential of switchgrass plants engineered with NfsI .
研究领域:
植物学
·
环境科学
·
遗传工程
✓ 已验证
DOI
高影响因子
CHINESE JOURNAL OF CHEMISTRY
·
2024
·
IF 5.5
Ximeng Shi,Yumeng Wang,Jiaoyang Yu,Yating Yang,Zecheng Jin,Hanghang Wang,Dalei Wu,Wei Chen,Jianming Guo,Yinan Zhang
Comprehensive Summary The detection of critical endogenous species, such as bacteria in microenvironments in the body, requires better imaging tools for visualization and monitoring of biological events. Bioluminescence imaging is the most popular strategy for obtaining real-time in living cells and organisms. Herein, we introduced a nitroaryl group on the C-3 position and a hydroxy group at the C-6 phenyl ring on furimazine to report the first bioluminescent probe ( 7 ) based on NanoLuc-furimazine bioluminescent pair for the detection of nitroreductase in bacteria. The probe, which possessed up to 560-fold intensity increase with a low detection limit of 16 ng/mL of nitroreductase, has the most efficient uncage efficiency in comparison with other bioluminescent congeners, thus enabling highly selective and sensitive visualization of NTR activity in a panel of clinical priority pathogens. Additionally, imaging of the recombinant strain as well as the NTR from mouse feces indicated the potential of this probe in the application of different mouse disease models.
研究领域:
生物化学
·
分子生物学
·
医学影像学
✓ 已验证
DOI
高影响因子
NANOTECHNOLOGY
·
2022
·Vol. 33
·期 21
·210001
·
IF 3.953
Yiwen Chen,Junguo He,Peigen Jiang,Heliang Pang,Xuhui Hu,Jie Zhang,Wenjing Zhang
The growing chloramphenicol (CAP) in wastewater brought a serious threat to the activity of activated sludge and the spread of antibiotics resistance bacteria. In this study, a highly ordered nanoporous Co3O4 layer on Co foil through anodization was prepared as cathode for nitro-group reduction and electrodeposited with Pd particles for dechlorination to reduce CAP completely. After 3 h treatment, almost 100% of CAP was reduced. Co2+ ions in Co3O4 served as catalytic sites for electrons transfer to CAP through a redox circle Co2+–Co3+–Co2+, which triggered nitro-group reduction at first. With the presence of Pd particles, more atomic H* were generated for dechlorination, which increased 22% of reduction efficiency after 3 h treatment. Therefore, a better capacity was achieved by Pd/Co3O4 cathode (K = 0.0245 min−1, K is reaction constant) than by other cathodes such as Fe/Co3O4 (K = 0.0182 min−1), Cu/Co3O4 (K = 0.0164 min−1), and pure Co3O4 (K = 0.0106 min−1). From the proposed reaction pathway, the ultimate product was carbonyl-reduced AM (dechlorinated aromatic amine product of CAP) without antibacterial activity, which demonstrated this cathodic technology was a feasible way for wastewater pre-treatment.
研究领域:
环境科学
·
化学工程
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
ANALYST
·
2014
·Vol. 140
·期 2
·574-581
·
IF 3.906
Jian Xu,Shaobo Sun,Qian Li,Ying Yue,Yingdong Li,Shijun Shao
A novel “Turn-On” fluorescent probe, quaternarized 4-pyridinyl-substituted BODIPY dye by incorporating a 5-nitrofuran moiety, was developed and applied for imaging the hypoxic status of tumor cells by the indirect detection of nitroreductase. The design was based on a nitroreductase-catalyzed reduction of the nitrofuran moiety in the presence of reduced nicotinamide adenine dinucleotide (NADH) as an electron donor and followed by the 1,6-rearrangement-elimination and the release of free 4-pyridinyl-substituted BODIPY dye 2. This probe displayed desired properties such as high specificity, “Turn-On” fluorescence response with suitable sensitivity, appreciable water solubility and rapid response time (within 5 min). Moreover, as a biocompatible molecule, the probe has been successfully applied for imaging the hypoxic status of tumor cells (e.g. A549 cells) and especially used for real-time determination of nitroreductase produced by Escherichia coli. Therefore, we hope to apply this novel method in the biomedical research fields for the imaging of disease-relevant hypoxia and detection of pathogenic microorganisms.
研究领域:
生物化学
·
医学影像
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
TALANTA
·
2019
·
IF 4.916
Lei Zhang,Leilei Guo,Xue Shan,Xiaohong Lin,Tingting Gu,Jikang Zhang,Junliang Ge,Wendi Li,Haixiong Ge,Qing Jiang,Xinghai Ning
Listeria monocytogenes ( Listeria ) is a facultative pathogenic bacterium, and a sensitive method for specific detection of Listeria is considered of clinically significant. However, current approaches for identifying Listeria are time consuming or tentative, and especially, cannot identify bacterial viability and antibiotic efficacy, which are critical in establishing a treatment recipe. Herein, we have developed a nitroreductase (NTR) responsive fluorescent probe (NRFP) with a fluorescence off-on feature, which could rapidly detect Listeria in vitro and in vivo with high specificity and sensitivity. NRFP showed a selective response to NTRs over other biological reductants, and could detect NTRs as low as 12.5 ng/mL. Furthermore, NRFP responded rapidly to NTRs within 10 min, enabling it real-time monitoring NTR production. Most importantly, NRFP could not only distinguish Listeria from other bacteria in vitro and in vivo for the first time, but could provide valuable information about Listeria desired for healthcare professionals, such as the presence and viability. Particularly, NRFP could real-time monitor antimicrobial effects in vivo , thereby identifying effective antibiotics for Listeria infections. Overall, NRFP appears to be an ideal imaging probe for Listeria , and possesses great potentials in diagnostic and therapeutic applications.
研究领域:
微生物学
·
医学影像
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CHEMICAL RESEARCH
·
2024
·
IF 1
Yinuo Wang,Yan Liang,Yutong Li,Yue Zhang,Haiwen Song,Aibing Ke
Furfural and nitromethane were utilized as raw materials for the synthesis of the herbicide-safe agent Furilazole through the Henry reaction, nitro reduction and addition-cyclization-acylation. A comprehensive investigation into the involved reaction processes was conducted, leading to the identification of barium hydroxide octahydrate as the catalyst for the Henry reaction. The continuous use methodology of the excess catalyst was determined through TGA/DSC curve analysis, and a rational purification method for Henry reaction products was proposed. The nitro reduction reaction employed Pd/C catalysis, while the subsequent addition-cyclization-acylation reaction was achieved in a single step. Five impurities affecting the reaction process were identified, and their potential mechanisms of formation were postulated. Optimization of synthetic process conditions was carried out for all involved reactions. The structures of intermediates, impurities, and products were characterized using NMR, HRMS, TGA/DSC and FTIR.
研究领域:
化学合成
·
农药科学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）