Immobilized beta2-adrenergic receptor: A powerful chromatographic platform for drug discovery and evaluation of drug-like property for natural products

Zheng, Xinxin; Fan, Hushuai; Song, Ze; Cheng, Peng; Jiang, Hongmei; Shi, Wei; Xiao, Chaoni; Wang, Jing; Li, Qian; Yin, Guowei; Zhao, Xinfeng

doi:10.1016/j.chroma.2021.462635

Cited by 8 publications

(1 citation statement)

References 40 publications

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“…Since the first synthesization by Wainer's group for drug-receptor interaction analysis [15], the receptor stationary phase has been dramatically improved and optimized for drug discovery purposes. i) The receptors were immobilized via site-directed covalent methods rather than physical adsorption/weak affinity/random covalent methods to improve the stability of the receptor [16]; ii) The receptors were immobilized via bioorthogonal reactions to avoid the tedious purification steps [17][18][19]; iii) The receptors were immobilized via small tags like unnatural amino acid to improve the activity of the receptors [20]; iv) A series of methods (e.g., nonlinear chromatography, adsorption energy distribution, and injection amount dependent methods) [21][22][23] and parameters (binding efficiency index and surface efficiency index) [24] were introduced to evaluate the drug-like property of natural products rapidly. As an important quantitative metric for drug-like property evaluation, the kinetic data could reflect the time-dependent changes of ligand-receptor complex, thus, highly related to the druggability of a ligand [25].…”

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confidence: 99%

Rapid separation and binding configuration prediction of the components in Danshen decoction to endothelin A receptor using affinity chromatography and molecular dynamics simulation

Zhang

et al. 2023

J of Separation Science

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As a famous traditional Chinese formula, Danshen Decoction has the potential to relieve the pain of pulmonary arterial hypertension patients, however, the functional components remain unknown. Herein, we reported a method to screen the functional components in Danshen Decoction targeting endothelin receptor A, an accepted target for the treatment of the disease. The receptor was functionalized on the macroporous silica gel through an epidermal growth factor receptor fusion tag and its covalent inhibitor. Using the affinity gel as the stationary phase, the bioactive compound was identified as salvianolic acid B by mass spectrometry. The binding kinetic parameter (dissociation rate constants k d ) of salvianolic acid B with the receptor was determined via peak profiling. Using the specific ligands of the receptor as probes, the binding configuration prediction of salvianolic acid B with the receptor was performed by molecular dynamics simulation. Our results indicated that salvianolic acid B is a potential bioactive compound in Danshen Decoction targeting the receptor. This work showed that receptor chromatography in combination with molecular dynamics simulation is applicable to predicting the binding kinetics and configuration of a ligand to a receptor, providing crucial insight for the rational design of drugs that recognize functional proteins.

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