JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Yahong Tan,Jinyue Yang,Min Wang,Qi Peng,Yongqi Li,Lifeng Fu,Mengmeng Zhang,Jiang Wu,Guanya Yang,Christopher John Hipolito,Youming Zhang,Jianxun Qi,Yi Shi,Yizhen Yin
Macrocyclic peptides have garnered significant attention as promising drug candidates. However, they typically face challenges in achieving and enhancing cell permeability for access to intracellular targets. In this study, we focused on the de novo screening of macrocyclic peptide inhibitors against the main protease (Mpro) of SARS-CoV-2 and identified novel noncovalently bound macrocyclic peptides that effectively inhibit proteolytic activity. High-resolution crystal structures further revealed molecular interactions between the macrocyclic peptides and Mpro. Subsequently, a specific macrocyclic peptide lacking cell permeability was further optimized and transformed into a low-toxicity, metabolically stable bicyclic peptide with a cell penetration capacity and therapeutic potential against SARS-CoV-2. The bicyclic peptide was achieved using a novel strategy that involved introducing both a bicyclic structure and a bridging perfluorobiphenyl group. Our study not only provides a lead peptide inhibitor for COVID-19 but also offers valuable insights into achieving cell penetration for macrocyclic peptides through strategic modifications.
研究领域:
药理学
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病毒学
·
药物发现
·
蛋白质工程
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DOI
高影响因子
APPLIED CATALYSIS B-ENVIRONMENTAL
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2018
·
IF 11.698
Tong-Yang Song,Zhao-Xia Dong,Jian-Dong Song,Xiao-Xia Wang,Guan-Qun Xie,Meng-Fei Luo,Ji-Qing Lu
Dehydrochlorination of 1, 1, 2-trichloroethane was performed on SiO 2 supported alkali metal (Na. K, Cs) and transition metal (Mn, Ni, Zn) catalysts. The surface basicity or acidity of the catalyst exerted great influence on catalytic behaviors. The catalysts with higher amount of base or acid sites resulted in higher activity due to more adsorption sites for reactant. The basic catalysts (Cs/SiO 2 and K/SiO 2 ) tended to form vinylidene chloride with a selectivity up to 80 %; the neutral catalysts (Na/SiO 2 and SiO 2 ) tended to form 1, 2-dichloroethene with a selectivity up to about 80 %; the acidic catalysts (Zn/SiO 2 , Mn/SiO 2 and Ni/SiO 2 ) tended to form 1, 2-dichloroethene with a selectivity up to 96 %. Proposed reaction mechanisms included an E1cb mechanism with a carbanion intermediate on the basic catalysts, an E2 concerted mechanism on the neutral catalysts, and an E1 mechanism with a carbonium intermediate on the acidic catalysts.
研究领域:
化学工程
·
催化科学
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DOI
高影响因子
CHEMICAL ENGINEERING SCIENCE
·
2025
·
IF 4.3
Shuang Sun,Yuefeng Deng,Ji Chen,Rui Qin,Zhongte Du,Qianshun Wen,Yang Meng
With the amid surging demand for lithium, solvent extraction has gradually developed into a key method for lithium recovery in industry. Due to the problems of large dissolution loss and high extraction equilibrium pH of β -diketone system, di-(2-ethylhexyl) phosphinic acid (P227) was selected to recover Li + from the desorption solution of salt lakes (SL-DS). Compared with di-2-ethylhexyl phosphoric acid (P204), 2-ethylhexyl phosphoric acid mono 2-ethylhexyl ester (P507), and bis (2,4,4-trimethylpentyl) phosphinic acid (Cyanex272), P227 showed better separation ability for Li + and Na + . The extraction conditions, including saponification degree, initial pH, extractant concentration and phase ratio were studied. It could be found that the extraction efficiency of Li + was maintained at a high level in the initial pH range of 2.25–12.61. A cascade process consisting of eight-stage extraction and five-stage scrubbing was performed to verify the feasibility of this technology. 99.9 % of Li + from the SL-DS was extracted at the equilibrium pH of 7.60, and P227 exhibited superior selectivity for Li + over Na + . Moreover, under the optimal condition of 3.8 mol/L HCl and O/A of 20:1, the stripping ratio of Li + reached 99.76 % via a four-stage stripping experiment. The Li + concentration of stripping liquor attained 23.11 g/L and a high-purity (99.5 %) Li 2 CO 3 product was obtained by precipitation. After five cycles, P227 demonstrated excellent regeneration stability. Eventually, the composition of extraction complex was revealed as LiR•NaR by slope analysis, and the cation exchange mechanism was further confirmed using FT-IR and 31 P NMR.
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产品关联
DOI
高影响因子
CHEMOSPHERE
·
2020
·
IF 5.778
Worku Lakew Kebede,Dong-Hau Kuo,Fekadu Tadesse Bekena,Lalisa Wakjira Duresa
Environmentally toxic organic pollutants, namely methylene blue (MB), neutral red (NR), Rhodamine B (RhB), and methyl orange (MO) dyes contain highly toxic, carcinogenic, non-biodegradable, and colored pigments which cause harm for humans and aquatic organisms even at low concentrations. To detoxify these toxic organic pollutants from the wastewater, the bimetallic solid solution-typed In–Mo(O,S) 2 catalyst with various indium (In) contents were synthesized at low temperature through a simple precipitation method. The morphological, structural, chemical compositions, electrochemical and optical properties of the catalysts were thoroughly characterized. The photodegradation performance of the In–Mo(O,S) 2 catalysts over the cationic, anionic and neutral dyes were studied under visible light irradiation. It has been observed that the photocatalytic activity was enhanced as In was added to the Mo(O,S) 2 catalyst, and In–Mo(O,S) 2 -20 was found to be the best composition to completely degrade four organic dyes. The dye degradation had rate constant values of 9.5 × 10 −2 min −1 , 6.3 × 10 −2 min −1 , 4.4 × 10 −2 min −1 , and 15.7 × 10 −1 min −1 for MB (20 ppm), NR (20 ppm), RhB (10 ppm), and MO (10 ppm) dyes, respectively. The active species for degradation of MB is different from those for RhB and MO. Single phase In–Mo(O,S) 2 -20 capable to degrade four kinds of dyes at a fast rate is a good photocatalyst.
研究领域:
环境科学
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材料科学
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DOI
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
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2016
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IF 2.618
Xia Wu,Jian-Cheng Zhu,Yu Zhang,Wei-Min Li,Xiang-Lu Rong,Yi-Fan Feng
Potential impact of lipid research has been increasingly realized both in disease treatment and prevention. An effective metabolomics approach based on ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS) along with multivariate statistic analysis has been applied for investigating the dynamic change of plasma phospholipids compositions in early type 2 diabetic rats after the treatment of an ancient prescription of Chinese Medicine Huang-Qi-San. The exported UPLC/Q-TOF-MS data of plasma samples were subjected to SIMCA-P and processed by bioMark, mixOmics, Rcomdr packages with R software. A clear score plots of plasma sample groups, including normal control group (NC), model group (MC), positive medicine control group (Flu) and Huang-Qi-San group (HQS), were achieved by principal-components analysis (PCA), partial least-squares discriminant analysis (PLS-DA) and orthogonal partial least-squares discriminant analysis (OPLS-DA). Biomarkers were screened out using student T test, principal component regression (PCR), partial least-squares regression (PLS) and important variable method (variable influence on projection, VIP). Structures of metabolites were identified and metabolic pathways were deduced by correlation coefficient. The relationship between compounds was explained by the correlation coefficient diagram, and the metabolic differences between similar compounds were illustrated. Based on KEGG database, the biological significances of identified biomarkers were described. The correlation coefficient was firstly applied to identify the structure and deduce the metabolic pathways of phospholipids metabolites, and the study provided a new methodological cue for further understanding the molecular mechanisms of metabolites in the process of regulating Huang-Qi-San for treating early type 2 diabetes.
研究领域:
代谢组学
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中医药学
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生物信息学
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DOI
高影响因子
JOURNAL OF SOL-GEL SCIENCE AND TECHNOLOGY
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2013
·Vol. 67
·期 3
·442-450
·
IF 1.66
Gong Cheng-Bin,Yang Yu-Zhu,Gao Chao,Tang Qian,Chow Cheuk-Fai,Peng Jing-Dong,Lam Michael Hon-Wah
Abstract
The primary objective of this work is to develop a photo - responsive surface molecularly imprinted polymer (SMIP) for 2,4 - dichlorophenoxyacetic acid (2,4 - D) to overcome the shortcomings of conventional molecularly imprinted polymers. A photo - responsive functional monomer was firstly prepared by covalent connecting azobenzene and 2,4 - D. The photo - responsive SMIP was then prepared on SiO 2 nanoparticles via sol–gel process, and 2,4 - D was removed via hydrolysis in acid. The SMIP shows specific affinity to 2,4 - D and reversible uptake and release of 2,4 - D upon alternate irradiation at 365 and 440 nm, respectively. The favorable binding strength of the imprinted receptor sites in the SMIP for 2,4 - D is found to be 2.51 × 10 4 M −1 . Density of receptor sites in the SMIP material is 10.59 μmol/g SMIP. The SMIP requires a shorter time to reach equilibrium than does the conventional molecularly imprinted polymer. The well - defined core - shell structure was clearly visualized by high resolution transmission electron microscopy. Graphical Abstract
研究领域:
材料科学
·
环境科学
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DOI
高影响因子
ORGANIC PROCESS RESEARCH & DEVELOPMENT
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2022
·
IF 3.858
Ling He,Wenjie Ye,Youyu Xie,Qinghai Liu,Hualei Wang,Dongzhi Wei
Bioreductions catalyzed by ketoreductases play an important role in the synthesis of chiral alcohols. However, the synthesis of (R)-2-chloro-1-(3,4-difluorophenyl)ethanol (24b), an important chiral intermediate for the synthesis of the anticoagulant ticagrelor, poses significant challenges in terms of high substrate concentration requirements that limit its production. In this study, a novel NADH-dependent, short-chain dehydrogenase, PpKR8, from Paraburkholderia phymatum STM815, exhibited excellent enantioselectivity and high activity for the production of (R)-CFPL (24b) through the reduction of 2-chloro-1-(3,4-difluorophenyl)ethanone (24a). The coexpression of PpKR8 and glucose dehydrogenase from Bacillus subtilis in Escherichia coli allowed up to 300 g/L (1.57 M) CFPO (24a) to be completely converted into 24b with 99.9% enantiomeric excess and a high space–time yield (728 g/(L day)). Substrate specificity assays demonstrated a broad substrate spectrum for PpKR8, which included 35 α/β-ketoesters, aromatic ketones, and heterocyclic ketones. Moreover, three additional optically pure chiral alcohols that are used as important drug intermediates were synthesized at high substrate concentrations (150–330 g/L), demonstrating the excellent industrial potential of PpKR8-mediated bioreductions.
研究领域:
生物化学
·
酶工程
·
制药工业
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DOI
高影响因子
APPLIED SURFACE SCIENCE
·
2021
·
IF 6.707
Jinhua Lai,Feng Cheng,Shuolin Zhou,Sha Wen,Dongwen Guo,Wenguang Zhao,Xianxiang Liu,Dulin Yin
Nitrogen-containing polymer-supported Cu-doped MnO 2 (Cu-MnO 2 @PDVTA) nanowires were prepared and their catalytic performances were evaluated via oxidation of biomass-derived 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA). The Cu-MnO 2 @PDVTA catalysts were characterized by Fourier-transform infrared spectroscopy, X-ray diffraction, N 2 physical adsorption, transmission electron microscopy, and X-ray photoelectron spectroscopy. Both the Cu 2+ and MnO 2 nanoparticles were found to synergistically promote HMF oxidation to FDCA via 2,5-furandicarbaldehyde and 5-formyl-2-furancarboxylic acid intermediates. The Cu-MnO 2 @PDVTA-3 catalyst demonstrated the highest catalytic activity, providing FDCA with an excellent yield of 96.8% after 12 h at 80 °C. The time course of HMF oxidation revealed that oxidation of the hydroxyl group in HMF was easier than that of the aldehyde group. Cu-MnO 2 @PDVTA-3 could act as a reusable heterogeneous catalyst for HMF oxidation.
研究领域:
化学工程
·
材料科学
·
催化反应
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DOI
高影响因子
JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY
·
2024
·
IF 1.5
He Xuexiang,Liao Linyuan,Tang Jing,Chen Lifeng,Lv Lidan,He Dongqiao,Yin Xiangbiao,Li Wenlong,Ning Shunyan,Wei Yuezhou
A silica-supported copolymer loaded with bis (2-ethylhexyl) phosphate was prepared and first investigated for the separation of trace radium from natural 232 Th. Results showed that the adsorbent was prepared successfully with ultrahigh selectivity and ultrafast adsorption kinetics towards thorium, making the separation easy and convenient. The chemical recovery rate to radium reached 96.7%, and the decontamination factor to thorium exceeded 10 5 . Generally, this work demonstrated the feasibility of using this material and method to directly separate 228 Ra and 224 Ra from 232 Th, rendering it significant in the future preparation and application of 212 Pb.
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产品关联
DOI
高影响因子
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
·
2020
·
IF 3.573
Xingang Li,Qingyu Zhang,Hong Li,Xin Gao
To solve the problem of catalyst recovery, high investment, and high energy consumption in the traditional manufacturing process of triethylene glycol di-2-ethylhexoate (TGDE), sulfated zirconia (HND-32) and reactive distillation (RD) were used in this work. Kinetics experiments for the esterification of triethylene glycol and 2-ethylhexanoic acid catalyzed by sulfated zirconia were performed at 463.15–493.15 K. The pseudo-homogeneous model was used to obtain the kinetics equation. Then, the process analysis results of the RD column indicate that there is an optimal theoretical plate number of the stripping section to obtain the highest yield of TGDE. The yield of TGDE can be enhanced to 98.15%, and 98.5 wt % TGDE can be obtained in the bottom of the RD column when the feed molar ratio is the stoichiometric ratio.
研究领域:
化学工程
·
催化化学
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DOI
高影响因子
ACS Applied Materials & Interfaces
·
2018
·
IF 8.097
Weiwei Mao,Haiping He,Pengcheng Sun,Zhizhen Ye,Jingyun Huang
A facile and scalable in situ microelectrolysis nanofabrication technique is developed for preparing cross-linked Ni(OH)2 nanosheets on a novel three-dimensional porous nickel template (Ni(OH)2@3DPN). For the constructed template, the porogen of NaCl particles not only induces a self-limiting surficial hot corrosion to claim the “start engine stop” mechanism but also serves as the primary battery electrolyte to greatly accelerate the growth of Ni(OH)2. As far as we know, the microelectrolysis nanofabrication is superior to the other reported Ni(OH)2 synthesis methods due to the mild condition (60 °C, 6 h, NaCl solution, ambient environment) and without any post-treatment. The integrated Ni(OH)2@3DPN electrode with a highly suitable microstructure and a porous architecture implies a potential application in electrochemistry. As a proof-of-concept demonstration, the electrode was employed for nonenzymatic glucose sensing, which exhibits an outstanding sensitivity of 2761.6 μA mM–1 cm–2 ranging from 0.46 to 2100 μM, a fast response, and a low detection limit. The microelectrolysis nanofabrication is a one-step, binder-free, entirely green, and therefore it has a distinct advantage to improve clean production and reduce energy consumption.
研究领域:
材料科学
·
电化学
·
生物医学工程
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DOI
高影响因子
ANIMAL FEED SCIENCE AND TECHNOLOGY
·
2016
·
IF 1.713
Q. Liu,C. Wang,Y.L Zhang,C.X. Pei,S.L Zhang,H.Q. Li,G. Guo,Y.J. Huo,W.Z. Yang,H. Wang
The objective of this study was to evaluate the effects of 2-methylbutyrate supplementation on growth performance and rumen development in pre- and post-weaned dairy calves. Fifty-six Chinese Holstein male calves with 15 days of age and 46.5 ± 0.37 kg of body weight (BW) were randomly assigned to one of four groups. The treatments were: control, low-2-methylbutyrate (LMB), moderate-2-methylbutyrate (MMB) and high-2-methylbutyrate (HMB) with 0, 3, 6 and 9 g 2-methylbutyrate per calf per day, respectively. Supplemental 2-methylbutyrate was hand- mixed into milk in pre-weaned calves and the concentrate portion of post-weaned calves. The study lasted 75 days, including a 15-day adaptation period and followed by a 60-day sampling period. Calves were weaned at 60 days of age. Six calves were chosen from each treatment at random and slaughtered at 30 and 90 days of age. Body weight, dry matter (DM) intake and stomach weight were measured, samples of ruminal tissues and blood were determined. DM intake increased linearly (P < 0.03) for post-weaned calves and overall DM intake with increasing 2-methylbutyrate supplementation and was higher for MMB and HMB than for LMB and control (P < 0.05). Average daily gain (ADG) increased linearly (P < 0.05) for pre-weaned calves, post-weaned calves and overall ADG with increasing 2-methylbutyrate supplementation, and was higher for MMB and HMB than for LMB and control (P < 0.05). Total stomach weight for pre- and post-weaned calves increased linearly (P < 0.05) and was higher for MMB and HMB than for LMB and control (P < 0.05). The ratio of rumen weight to total stomach weight tended to increase linearly (P = 0.055) for pre-weaned calves and increased linearly (P = 0.019) for post-weaned calves, whereas the ratio of abomasum weight to total stomach weight decreased linearly (P < 0.05) for pre-weaned calves and post-weaned calves with increasing 2-methylbutyrate supplementation. The ratio of total stomach weight to body weight for pre-weaned calves and post-weaned calves increased linearly (P < 0.05) and was higher for MMB and HMB than for LMB and control (P < 0.05). Both the length and width of rumen papillae, and the relative expression of mRNA for growth hormone receptor (GHR) and 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) in rumen mucosa tended to increase linearly for pre-weaned calves, but increased linearly (P < 0.05) for post-weaned calves and was higher for MMB and HMB than for LMB and control (P < 0.05). Blood concentrations of BHBA increased linearly (P < 0.05) for post-weaned calves with increasing 2-methylbutyrate supplementation and was higher for MMB and HMB than for LMB and control (P < 0.05). Blood concentrations of GH and IGF-1 increased linearly (P < 0.05) for pre- and post-weaned calves with increasing 2-methylbutyrate supplementation and was higher for MMB and HMB than for LMB and control (P < 0.05). The present results indicated that 2-methylbutyrate accelerated growth of calves by improving rumen development and its ketogenesis. The 2-methylbutyrate stimulates the growth performance and rumen development of dairy calves in a dose-dependent manner. In the experimental conditions of this trial, the optimum 2-methylbutyrate dose was about 6.0 g 2-methylbutyrate per calf per day.
研究领域:
动物科学
·
营养学
·
反刍动物生理学
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DOI
高影响因子
危险品化学品经营许可证（带存储）