9 results on '"Xinfeng Zhao"'
Search Results
2. Development of immobilized beta1-adrenoceptor chromatography for rapid discovery of ligands specifically binding to the receptor from herbal extract
- Author
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Aerduosi, Shayiranbieke, Qi, Liang, Taotao, Wang, Jing, Ma, Guoan, Li, Xiaoqian, Du, Guodong, Zhang, Chaozhan, Wang, and Xinfeng, Zhao
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ErbB Receptors ,Chromatography ,Escherichia coli Proteins ,Organic Chemistry ,Escherichia coli ,Receptors, Adrenergic, beta-2 ,General Medicine ,Receptors, Adrenergic, beta-1 ,Ligands ,Carbon-Oxygen Ligases ,Biochemistry ,Drugs, Chinese Herbal ,Analytical Chemistry - Abstract
The discovery of beta1-adrenoceptor (β
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- 2022
3. Site-selective covalently immobilized alpha 1A adrenergic receptor for thermodynamic and extra-thermodynamic study of four ligands binding to the receptor by chromatographic methods
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Xinyi, Yuan, Aerduosi, Shayiranbieke, Ru, Xu, Hongmei, Jiang, Yushan, Yang, Yajun, Zhang, Guowei, Yin, and Xinfeng, Zhao
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Tamsulosin ,Chromatography ,Receptors, Adrenergic, alpha-1 ,Organic Chemistry ,Thermodynamics ,General Medicine ,Ligands ,Biochemistry ,Analytical Chemistry - Abstract
Immobilized G protein-coupled receptor is a versatile tool to study ligand-receptor interactions. In this work, we synthesized the immobilized alpha 1A adrenergic receptor (α
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- 2022
4. Immobilized beta2-adrenergic receptor: A powerful chromatographic platform for drug discovery and evaluation of drug-like property for natural products
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Hongmei Jiang, Jing Wang, Wenhua Shi, Hushuai Fan, Qian Li, Chaoni Xiao, Guowei Yin, Xinfeng Zhao, Xinxin Zheng, Peixuan Cheng, and Ze Song
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Drug ,Chromatography ,Natural product ,Stemona ,biology ,Drug discovery ,Platycodin D ,High-throughput screening ,media_common.quotation_subject ,Organic Chemistry ,General Medicine ,biology.organism_classification ,Biochemistry ,Analytical Chemistry ,chemistry.chemical_compound ,chemistry ,Medicinal herbs ,Radix ,media_common - Abstract
Drug discovery based on natural products like medicinal herbs remains challenging due to the technique limitations for rapidly screening and validating leads. To address the challenges, we employ the immobilized β2- adrenergic recepotor (β2-AR), an identified target of asthma, as the stationary phase in chromatographic column to screen compounds extracted from Stemonae Radix, Playtycodonis Radix, and Glycyrrhizae Radix et Rhizoma. To analyze binding properties of the extracted compounds to the immobilized receptors, we measured their retention behavior in the receptor chromatography and compared with six clinical asthma drugs. We identified tuberostemonine, platycodin D, and glycyrrhizic acid as the potential leads against asthma by our β2-AR chromatography coupled with mass spectrum (MS). The association constants of the three compounds to β2-AR were 2.85 × 10−5, 2.55 × 10−4, and 4.07 × 10−6 M with the dissociation rate constants of 6.91 ± 0.35, 11.88 ± 0.60, and 9.49 ± 0.64 min−1, respectively. Tuberostemonine, a pentacyclic Stemona alkaloids, presented the most optimum values of binding efficiency index (BEI) and surface efficiency index (SEI) as close to the diagonal of SEI–BEI optimization plane when it is compared with platycodin D, glycyrrhizic and the six clinical drugs. Our results suggest that tuberostemonine is a promising natural product to be developed for treating asthma because it exhibits better drug-like binding properties to β2-AR than the clinical drugs. As such, we demonstrate a chromatographic strategy to identify bioactive natural products based on the β2-AR immobilization, which can be widely adopted to screen natural products from mixture of herbal extracts.
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- 2021
5. Development and characterization of a selective chromatographic approach to the rapid discovery of ligands binding to muscarinic-3 acetylcholine receptor
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Jianping Ren, Xinfeng Zhao, Aerduosi Shayiranbieke, Qi Liang, Fang Cao, Xiaoying Fu, Xue Zhao, Ru Xu, and Xinyi Yuan
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Receptor, Muscarinic M3 ,Chromatography ,High-throughput screening ,Organic Chemistry ,Cholinergic Agents ,Muscarinic acetylcholine receptor M3 ,General Medicine ,Ligands ,Biochemistry ,Analytical Chemistry ,chemistry.chemical_compound ,chemistry ,Affinity chromatography ,Covalent bond ,Liquiritigenin ,Linker ,Protein Binding ,Haloalkane dehalogenase ,Acetylcholine receptor - Abstract
The pursuit of new ligands binding to muscarinic-3 acetylcholine receptor (M3R) is viewed as challenging due to the lack of screening methods with high efficiency. To address such challenges, this work developed and characterized an approach to the rapid discovery of M3R ligands using the immobilized receptor as the chromatographic stationary phase. We fused haloalkane dehalogenase (Halo) as a tag at the C-terminus of M3R. The fusion M3R was immobilized on 6-chlorocaproic acid-activated ammino-microspheres by the specific covalent reaction between the Halo-tag and the linker. Comprehensive characterizations of the immobilized M3R were performed by scanning electron microscope, X-ray photoelectron spectroscopy, and the investigation on the binding of three specific ligands to the receptor. The feasibility of the immobilized M3R in complex matrices was tested by screening the bioactive compounds in Zhisou oral liquid, assessing the interaction between the screened compounds and the receptor using zonal elution, and evaluating the in vivo activity of the targeted compounds. The results evidenced that the immobilized M3R has high specificity, good stability, and the capacity to separate M3R ligands from complex matrices. These allowed us to identify naringin, hesperidin, liquiritigenin, platycodin D, and glycyrrhizic acid as the potential ligands of M3R. The association constants of the five compounds to M3R were 4.44 × 104, 1.11 × 104, 7.20 × 104, 4.15 × 104, and 3.36 × 104 M−1. The synergistic application of the five compounds exhibited an equivalent expectorant activity to the original formula. We reasoned that the current method is possible to provide a highly efficient strategy for the discovery of receptor ligands.
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- 2021
6. Halo-tagged protein immobilization: Effect of halide linkers on peak profile and drug-protein interaction
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Qi Liang, Ru Xu, Xin Wen, Xiaoying Fu, Jing Wang, Xinfeng Zhao, Yan Xue, Haiyue Zuo, Gangjun Feng, and Linkang Li
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Drug ,Time Factors ,media_common.quotation_subject ,Halide ,Biochemistry ,Chromatography, Affinity ,Analytical Chemistry ,Acetic acid ,chemistry.chemical_compound ,Halogens ,Histidine ,media_common ,Chromatography ,Protein immobilization ,Organic Chemistry ,General Medicine ,Combinatorial chemistry ,Kinetics ,Immobilized Proteins ,Nonlinear Dynamics ,Pharmaceutical Preparations ,chemistry ,Covalent bond ,Alkoxy group ,Receptors, Adrenergic, beta-2 ,Linker - Abstract
In previous work, we have established a one-step method to immobilize halo-tagged proteins onto microspheres through the covalent bond formed between the halo-tag and the halide linkers on the support surface. We observe extremely tailed peaks of most of drugs on the immobilized proteins, which is reasoned by the nonspecific interaction between the linkers and the drugs. To prove this, the current work designed five different halide linkers for the immobilization of beta2-adrenoceptor (β2-AR). We applied the immobilized receptor to systematically realize the effects of these halide linkers on drug-receptor interaction by analyzing peak profiles of five drugs. The retention times and the half-widths of the drugs appeared to be negatively correlated to the atom numbers of the linkers in the range of 6–13 atoms. Subsequent increase of linker atoms resulted in reduced retention times and wider peaks of the drugs. Applying identical linker length, we observed clear reduced retention times and half-widths of the five drugs than the linker in the absence of oxygen atom. Such improvement was dominated by the number of oxygen atoms. These indicated that linker S-4 (2-(2-(2-(2-chloroethoxy) ethoxy) ethoxy) acetic acid) was optimal to eliminate the unwanted non-specific interactions. In comparison with the columns prepared by linker S-1 (6-chlorocaproic acid) and histidine tagged β2-AR, the drugs on the linker S-4 column gave greater dissociation rate constants (e.g. 60.3±0.3 s-1 for salbutamol), which is closer to the data in literatures. Taking together, we concluded that optimization of the linker structure plays particular role in reducing the non-specific interaction between the immobilized protein and the drugs, thereby making the determination of drug-protein interaction more reliable.
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- 2021
7. G protein-coupled receptor-in-paper, a versatile chromatographic platform to study receptor-drug interaction
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Qian Li, Xinfeng Zhao, Gangjun Feng, Xinyi Yuan, Xiaoying Fu, Ping Li, Jing Wang, Rui Tian, Zhaoling Hou, and Zhongman Chang
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Chromatography, Paper ,Ligands ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Analytical Chemistry ,Affinity chromatography ,X-ray photoelectron spectroscopy ,GTP-Binding Proteins ,Terbutaline ,Albuterol ,Drug Interactions ,Fourier transform infrared spectroscopy ,Chromatography ,Chemistry ,Elution ,010401 analytical chemistry ,Organic Chemistry ,General Medicine ,Fluorescence ,0104 chemical sciences ,Paper chromatography ,Membrane ,Elemental analysis ,Adsorption ,Receptors, Adrenergic, beta-2 - Abstract
High-performance affinity chromatography is limited by its high cost and high pressure. Paper is made up of porous fiber networks and has the properties of low cost, ease of fabrication, and biodegradable. Due to these advantages, herein, we immobilized beta2-adrenoceptor (β2-AR) onto the surface of the polytetrafluoroethylene membrane, a paper-based material, and constructed a G protein-coupled receptor (GPCR)-in-paper chromatographic platform. This platform was characterized by Fourier transform infrared spectroscopy, fluorescence analysis, X-ray photoelectron spectroscopy, and chromatographic studies. These morphological and elemental analysis showed that β2-AR was successfully immobilized on the paper surface. The specific drugs have good retentions on the GPCR-in-paper chromatographic platform. The association constants of salbutamol, terbutaline and bambuterol to β2-AR were calculated to be 2.02 × 104 M−1, 1.15 × 104 M−1, 1.75 × 104 M−1 by adsorption energy distribution, which were in good line with the values from frontal analysis, zonal elution and previous literatures. We demonstrated that the GPCR-in-paper platform was cost-effective, easy to be modified for protein immobilization, and applicable in the receptor-drug interaction analysis. We believe such a platform sheds new light on paper chromatography for receptor-drug interaction analysis and other applications.
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- 2021
8. Reversible and site-specific immobilization of β2-adrenergic receptor by aptamer-directed method for receptor-drug interaction analysis
- Author
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Rui Tian, Faizan Ahmad, Qi Liang, Xinfeng Zhao, Juan Gao, Zhongman Chang, Xiaoni Jia, and Ping Li
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Chromatography ,Tulobuterol ,Methoxyphenamine ,Aptamer ,Ligand binding assay ,010401 analytical chemistry ,Organic Chemistry ,General Medicine ,010402 general chemistry ,Ligand (biochemistry) ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,Analytical Chemistry ,chemistry.chemical_compound ,chemistry ,medicine ,Biophysics ,Binding site ,Receptor ,G protein-coupled receptor ,medicine.drug - Abstract
Immobilized protein makes a profound impact on the development of assays for drug discovery, diagnosis and in vivo biological interaction analysis. Traditional methods are enormously challenged by the G-protein coupled receptor ascribed to the loss of receptor functions. We introduced a β2-adrenergic receptor (β2-AR) aptamer into the immobilization of the receptor. This was achieved by mixing the receptor conjugated silica gel with cell lysates containing the receptor. We found that the aptamer-directed method makes immobilized β2-AR good stability in seven days and high specificity of ligand recognition at the subtype receptor level. Feasibility of the immobilized β2-AR in drug-receptor interaction analysis was evaluated by injection amount-dependent method, nonlinear chromatography, and peak decay analysis. Salbutamol, methoxyphenamine, ephedrine hydrochloride, clorprenaline, tulobuterol, bambuterol, propranolol and ICI 118551 bound to the receptor through one type of binding sites. The association constants presented good agreement within the three methods but exhibited clear differences from the data by radio-ligand binding assay. Regarding these results, we concluded that the aptamer-directed method will probably become an alternative for reversible and site-specific immobilization of GPCRs directly from complex matrices; the immobilized receptor is qualitative for drug-receptor interaction analysis.
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- 2020
9. Exploring drug–protein interactions using the relationship between injection volume and capacity factor
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Zijian Li, Xinfeng Zhao, Jiejun Chen, Youyi Zhang, Liujiao Bian, Xiaohui Zheng, Jianbin Zheng, Chaoni Xiao, and Qian Li
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Ligands ,Biochemistry ,Chromatography, Affinity ,Analytical Chemistry ,Radioligand Assay ,chemistry.chemical_compound ,Affinity chromatography ,medicine ,Animals ,Humans ,Chromatography, High Pressure Liquid ,Serum Albumin ,Binding Sites ,Chromatography ,Methoxyphenamine ,Elution ,Organic Chemistry ,General Medicine ,Human serum albumin ,Ligand (biochemistry) ,Capacity factor ,Promethazine ,Dissociation constant ,Immobilized Proteins ,Models, Chemical ,Pharmaceutical Preparations ,chemistry ,Rabbits ,Receptors, Adrenergic, beta-2 ,medicine.drug - Abstract
Affinity chromatography is the most widespread and widely accepted methodology for exploring drug-protein and protein-protein interactions. Despite the successful application of frontal analysis and zonal elution in affinity chromatography, research into the creation of new mathematical tools for data processing is encouraged due to these two methods' drawbacks of long analysis times and high ligand consumption. In this work, we created a novel mathematical model using the relationship between the molar amount of an injected solute and its capacity factor. We validated the method by analyzing the binding of drugs to human serum albumin (HSA) and β2-adrenoceptor (β2-AR). The association constants of omeprazole, propranolol and promethazine binding to HSA were determined to be (4.10±0.24)×10(4), (2.30±0.12)×10(4) and (1.24±0.14)×10(4)M(-1), respectively. These constants agreed with previously reported literature results of 4.60×10(4), 2.30×10(4) and 1.40×10(4)M(-1). Salbutamol, norepinephrine, isoprenaline, bamethane and methoxyphenamine were found to bind to β2-AR with association constants of (1.11±0.06)×10(3), (0.95±0.03)×10(3), (1.66±0.12)×10(3), (0.47±0.04)×10(3) and (0.43±0.02)×10(3)M(-1), respectively, which positively correlated to the negative logarithm of the dissociation constants obtained via radio-ligand binding assays. The proposed model is relatively fast and conserves ligand, and it has the potential to serve as an alternative method for rapidly revealing drug-protein and protein-protein interactions.
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- 2014
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