MOLECULAR PHARMACOLOGY
·
2023
·Vol. 103
·期 4
·241-254
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IF 3.6
Jian Gao,Hao Yin,Yanqun Dong,Xintong Wang,Yani Liu,KeWei Wang
The uricosuric drug benzbromarone, widely used for treatment of gout, hyperpolarizes the membrane potential of airway smooth muscle cells, but how it works remains unknown. Here we show a novel role of benzbromarone in activation of large conductance calcium-activated K+ channels. Benzbromarone results in dose-dependent activation of macroscopic big potassium (BK) currents about 1.7- to 14.5-fold with an EC50 of 111 μM and shifts the voltage-dependent channel activation to a more hyperpolarizing direction about 10 to 54 mV in whole-cell patch clamp recordings. In single-channel recordings, benzbromarone decreases single BKα channel closed dwell time and increases the channel open probability. Coexpressing β1 subunit also enhances BK activation by benzbromarone with an EC50 of 67 μM and a leftward shift of conductance-voltage (G-V) curve about 44 to 138 mV. Site-directed mutagenesis reveals that a motif of three amino acids 329RKK331 in the cytoplasmic linker between S6 and C-terminal regulator of potassium conductance (RCK) gating ring mediates the pharmacological activation of BK channels by benzbromarone. Further ex vivo assay shows that benzbromarone causes reduction of tracheal strip contraction. Taken together, our findings demonstrate that uricosuric benzbromarone activates BK channels through molecular mechanism of action involving the channel RKK motif of S6-RCK linker. Pharmacological activation of BK channel by benzbromarone causes reduction of tracheal strip contraction, holding a repurposing potential for asthma and pulmonary arterial hypertension or BK channelopathies.
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ANALYTICA CHIMICA ACTA
·
2023
·
IF 6.2
Xiao-Dong Cheng,Zheng Zhang,Yun-Ping Li
Green chromatography techniques using low-toxic mobile phase are getting increasingly attention in recent years. The core is developing stationary phases that possess adequate retention and separation under the mobile phase of high content water. Using thiol-ene click chemistry, an undecylenic acid-bonded silica stationary phase (UAS) was prepared in a facile manner. Elemental analysis (EA), solid-state 13 C NMR spectroscopy and Fourier transform infrared spectrometry (FT-IR) confirmed the successful preparation of UAS . The synthesized UAS was employed for per aqueous liquid chromatography (PALC), which uses little organic solvent during separation. Due to the hydrophilic carboxy, thioether group and hydrophobic alkyl chains of the UAS, various categories of compounds (including nucleobases , nucleosides , organic acids and basic compounds) with different properties can achieve enhanced separation under the mobile phase of high content water compared with commercial C18 and silica stationary phases. Overall, our present UAS stationary phase shows excellent separation ability toward highly polar compounds and meets the requirements of green chromatography.
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ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Jieqing Feng,Qisheng Zhong,Ting Zhou
The online coupling technique of sample preparation with chromatography is a frontier topic in analytical chemistry since it minimizes errors caused by sample loss, shortens analysis time, and reduces solvent consumption. An online pressure change focusing-supercritical fluid selective extraction chromatography (PCF-SFSEC) technique was developed in this study, realizing extraction, purification, separation, and detection in a single run with only microliter-scale samples. The pressure change focusing strategy achieved column-head stacking by decreasing the dissolving capacity of the supercritical fluid, enabling the large volume introduction of extractants into supercritical fluid chromatography without causing peak broadening or distortion. All the extracts could be directly loaded into the chromatography system without split flow. Based on the supercritical fluid selective extraction (SFSE) strategy, the sorbents removed interferences and water from samples, effectively alleviating matrix effects and realizing the direct aqueous sample analysis. The efficiency of online PCF-SFSEC was demonstrated by the enantioselective analysis of 22 chiral drugs in rat plasma, covering eight categories with different pharmacological effects. The entire analysis took 25 min, consuming only 5 μL samples. All analytes in PCF-SFSEC obtained sharp and symmetrical peaks with resolutions higher than 1.0, and 86% had resolutions higher than 1.5. Limits of quantification (LOQs) ranged from 0.0600 to 32.1 μg/L. Recoveries were in the range of 75.8–117.2%. In addition, the developed approach obtained more satisfactory repeatability and significantly reduced matrix effects than conventional methods. The newly established online PCF-SFSEC technique is believed to be a green and powerful tool for the chiral analysis of complex samples.
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SENSORS AND ACTUATORS B-CHEMICAL
·
2021
·
IF 7.46
Yingjie Zhao,Li Tian,Xin Zhang,Zhuo Sun,Xiangyu Shan,Qian Wu,Ruizhan Chen,Juan Lu
A specificity recognition molecularly imprinted electrochemiluminescence sensor (MIECLS) for determination of clenbuterol (CLB) was established by molecular imprinting technology. In this sensing platform, Fe 2 O 3 was used as the carrier to fix Ru(bpy) 3 2+ , and it could also improve electrochemiluminescence (ECL) signal due to large specific surface area and better electronic transmission efficiency. The introduction of molecular imprinted membranes (MIPs) with CLB as template molecules realized the specificity identification of sensors. The intensity of the ECL signal decreased gradually when the concentration of CLB increased. Based on this characteristic, a novel method for measuring CLB was established, and the related mechanism was studied. Under the optimal conditions, the ECL response was proportional to the logarithm of CLB concentration in the range of 1 × 10 −9 mol L −1 to 1 × 10 −4 mol L −1 with a detection limit of 3.3 × 10 −10 mol L −1 . The results prove that MIECLS has great potential in pork and liver samples testing.
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MOLECULES
·
2018
·Vol. 23
·期 9
·2337
·
IF 3.098
Xixia Liu,Qi Lu,Sirui Chen,Fang Wang,Jianjun Hou,Zhenlin Xu,Chen Meng,Tianyuan Hu,Yaoyao Hou
We describe a multiple combined strategy to discover novel aptamers specific for clenbuterol (CBL). An immobilized ssDNA library was used for the selection of specific aptamers using the systematic evolution of ligands by exponential enrichment (SELEX). Progress was monitored using real-time quantitative PCR (Q-PCR), and the enriched library was sequenced by high-throughput sequencing. Candidate aptamers were picked and preliminarily identified using a gold nanoparticles (AuNPs) biosensor. Bioactive aptamers were characterized for affinity, circular dichroism (CD), specificity and sensitivity. The Q-PCR amplification curve increased and the retention rate was about 1% at the eighth round. Use of the AuNPs biosensor and CD analyses determined that six aptamers had binding activity. Affinity analysis showed that aptamer 47 had the highest affinity (Kd = 42.17 ± 8.98 nM) with no cross reactivity to CBL analogs. Indirect competitive enzyme linked aptamer assay (IC-ELAA) based on a 5′-biotin aptamer 47 indicated the limit of detection (LOD) was 0.18 ± 0.02 ng/L (n = 3), and it was used to detect pork samples with a mean recovery of 83.33–97.03%. This is the first report of a universal strategy including library fixation, Q-PCR monitoring, high-throughput sequencing, and AuNPs biosensor identification to select aptamers specific for small molecules.Keywords:clenbuterol;systematic evolution of ligands by exponential enrichment;real-time quantitative PCR;high-throughput sequencing technology;aptamers;gold nanoparticles biosensor
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JOURNAL OF CHROMATOGRAPHY A
·
2015
·
IF 4.169
Xiuzhen Qiu,Xian-Yan Xu,Yong Liang,Yongbiao Hua,Huishi Guo
In this paper, a method for the synthesis of ractopamine molecularly imprinted polymers (MIPs) nanotube membranes on anodic alumina oxide (AAO) nanopore surface by atom transfer radical polymerization (ATRP) was presented, in which methacrylic acid (MAA) was selected as functional monomer with a polymerization rate of 1:6 between ractopamine and MAA by the computational investigations. The morphology of MIPs nanotube membranes characterized by scanning electron microscope (SEM) suggested a well growth in the AAO nanopore surface. A series of adsorption experiments revealed that the MIPs nanotube membranes showed better extraction capacity and good selectivity for ractopamine and its analogues than that of non-imprinted polymers (NIPs) nanotube membranes. In order to evaluate the usability of the MIPs nanotube membranes, a methodology by combining MIPs nanotube membranes extraction couple with high performance liquid chromatography (HPLC) detection for the determination of β 2 -agonists in complex samples was developed. The linear ranges were 10–1000 μg/L for ractopamine, 100–1000 μg/L for clenbuterol, epinephrine and dopamine, and 200–1000 μg/L for terbutaline. The detection limits were within the range of 0.074–0.25 μg/L and the RSDs ( n = 3) were from 2.8% to 4.3%. The method was successfully applied to the analysis of β 2 -agonists in spiked real samples, The recoveries of all the β 2 -agonists at the two concentration levels were found to be within the range of 86.3–97.0% and 82.8–95.7%, respectively. The RSDs were within 2.7–5.7%. The results demonstrated that the proposed method is very suitable for the determination of β 2 -agonists in pork samples.
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TALANTA
·
2015
·
IF 3.545
Qing Wang,Yao Long,Lin Yao,Li Xu,Zhi-Guo Shi,Lanying Xu
A mixed-mode chromatographic stationary phase , C18-DTT (dithiothreitol) silica (SiO 2 ) was prepared through “thiol-ene” click chemistry. The obtained material was characterized by fourier transform infrared spectroscope, nitrogen adsorption analysis and contact angle analysis. Chromatographic performance of the C18-DTT was systemically evaluated by studying the effect of acetonitrile content, pH, buffer concentration of the mobile phase and column temperature. It was demonstrated that the novel stationary phase possessed reversed phase liquid chromatography (RPLC)/hydrophilic interaction liquid chromatography (HILIC) mixed-mode property. The stop-flow test revealed that C18-DTT exhibited excellent compatibility with 100% aqueous mobile phase. Additionally, the stability and column-to-column reproducibility of the C18-DTT material were satisfactory, with relative standard deviations of retention factor of the tested analytes (verapamil, fenbufen , guanine , tetrandrine and nicotinic acid) in the range of 1.82–3.72% and 0.85–1.93%, respectively. Finally, the application of C18-DTT column was demonstrated in the separation of non-steroidal anti-inflammatory drugs, aromatic carboxylic acids , alkaloids, nucleo-analytes and polycyclic aromatic hydrocarbons . It had great resolving power in the analysis of various compounds in HILIC and RPLC chromatographic conditions and was a promising RPLC/HILIC mixed-mode stationary phase.
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2016
·Vol. 408
·期 19
·5261-5268
·
IF 3.125
Liu Yixi,Wang Yong,Liu Le,He Yonghong,He Qinghua,Ji Yanhong
A method to detect small molecules with a molecularly imprinted polymer/quantum dot (MIP-QD) chip using a home-built optical fluidic system was first proposed in this study. Ractopamine (RAC) was used as the model molecule to demonstrate its feasibility. The sensing of the target molecule is based on the quenching amount of the quantum dots. The method is facile, cost-saving, easy for miniaturization and avoids the cumbersome steps that are needed to get the fluorescent quenching curve using a spectrofluorometer. Most importantly, more details and accurate response time can be obtained by use of this method. The experimental results show that the prepared chips with low cost are highly selective and the home-built detection system allows the fast binding kinetics. The recorded quenching process was used to study the kinetic uptake of RAC onto the MIP-QD chip and the specificity towards RAC. The system can further be utilized to study the effect of the solvent, pH and temperature on the selectivity of the prepared MIP. The methodology could be extended to other similar studies with different molecules.
Schematic illustration of the molecularly imprinted polymer/quantum dot chip capturing the target molecule
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CHEMICAL PHYSICS LETTERS
·
2017
·
IF 1.815
Shaopeng Qi,Bo Zhao,Bo Zhou,Xiaoqing Jiang
A new electrochemical immunosensor for fast determination of ractopamine (RAC) is fabricated based on pristine graphene (PG). The PG provides a microenvironment beneficial the immobilization of RAC, promotes the electron transfer, and raises the sensitivity of the immunosensor. The free RAC in solution can be effectively measured based on the competitive immunoreaction between RAC-antibody and RAC. The calibration graph shows linearity over the concentration ranges of 0.1–10 and 10–4000 ng mL −1 . The proposed immunosensor displays a satisfactory stability, selectivity, and reproducibility and has been applied to the quantificational detection of RAC in real pork samples.
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TALANTA
·
2024
·
IF 5.6
Yongjing Liu,Dongting Huang,Chenxi Zhuo,Min Guo,Lirong Chen,Xiaofen Chen,Hua Li,Wei Xu
A series of supramolecular deep eutectic solvents (SURPADESs) consisting of β -cyclodextrin ( β -CDs) ( β -CD, HP- β -CD, M- β -CD) and l -lactic acid were synthesized and employed as chiral selector to investigate their chiral selectivity in capillary electrophoresis. Key elements influencing the separation efficiency, such as the ratio of HBA/HBD of SUPRADESs, the concentration of SUPRADESs, and buffer pH were thoroughly examined and deliberated upon. Under the optimum enantioseparation conditions, three SUPRADESs systems showed markedly enhanced chiral separation of model chiral drugs, in comparison with single CDs and dual chiral selectors composed by adding its two constituents CDs and l -lactic acid separately. Additionally, the Benesi-Hildebrand plot was employed to determine the binding constant for the inclusion complexes, and molecular modeling was used to explore the mechanisms behind the increased chiral separations in SUPRADESs. Results demonstrated that SUPRADESs exhibit significantly improved chiral selectivity efficiency by enhancing the host-guest encapsulation of the constituent β -CDs, which is attributed to the increased hydrogen bonding and hydrophobic interactions between chiral analytes and β -CDs and HBD of SUPRADESs. This work provides a possibility for SUPRADESs to be used as chiral selection in CE.
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FOOD CHEMISTRY
·
2024
·
IF 8.5
Lu Yang,Tong Zhai,Jing Wang,Hong Zheng,Jing-Min Liu,Shuo Wang
To achieve high throughput detection of clenbuterol while reducing matrix interference, we developed a simple and integrated nano-inspection platform. Herein, based on the simplicity and convenience of paper chip, a multi-layer paper chip-chemiluminescence (CL) sensor was designed in the form of “48-well plate” type. The all-in-one paper chip-CL sensor has integrated the covalent organic frameworks (COFs) layer for sample matrix purification, high affinity nanobody layer for specific capture of target, and CL rapid response layer for the final determination. The signal readout was realized by the inhibitory effect of clenbuterol on the K 3 [Fe(CN) 6 ] CL system. Detection of clenbuterol in pork meat was verified by measuring the CL intensity and satisfactory recoveries (85.9 %–97.3 %) were achieved. 48 samples could be simultaneously detected on one-chip in one-test, favoring the high-throughput detection. Especially, the work explored a new pathway for design of portable analytical instruments to achieve immediate on-site detection of hazards.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Liang Luo,Chaochao Chen,Jincheng Xiong,Yanton Pan,Qiang Li,Xiaonan Wang,Sihan Wang,Jianzhong Shen,Zhanhui Wang
As the most widely used immunoassay, enzyme-linked immunosorbent assay (ELISA) relies on perishable enzymes and usually provides poor sensitivity and stability, limiting its application in detecting trace analytes in harsh environments. Herein, a new ratiometric fluorescence (RF) sensing platform enhanced by a nanozyme–enzyme cascade reaction composed of MnO2 nanosheets (MnO2 NSs) and alkaline phosphatase (ALP) was proposed. In this RF platform, the versatile MnO2 NSs worked as a robust oxidase-like nanozyme to catalyze nonfluorescent Amplex Red (AR) into fluorescent resorufin and as a quencher to quench the fluorescence of carbon dots (CDs). Given that ALP could catalyze ascorbic acid 2-phosphate (AAP) into ascorbic acid (AA), followed by AA reducing MnO2 NSs into Mn2+, resulting in the fluorescence of AR decrease but fluorescence of CD recovery simultaneously. The regulation of MnO2 NSs for the fluorescence intensity of AR (Em at 585 nm) and CDs (Em at 460 nm) could cascade with ALP-triggered reaction to construct an RF sensing platform based on RF signal (F585/F460) output. The proposed RF sensing platform could achieve a superior limit of detection (LOD) of 0.037 mU mL–1 for ALP activity quantification. Inspired by the excellent performance of the RF sensing platform, a sensitive and accurate RF ELISA for ractopamine (RAC) detection was established with an LOD of 0.029 ng mL–1, which was nearly 5.5 times more sensitive than traditional colorimetric ELISA. This RF sensing platform based on robust nanozyme-triggered enzymatic cascade signal amplification and excellent RF signal readout has offered a powerful and universal platform for RAC and other trace target detection.
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