Confirming therapeutic target of protopine using immobilized β2‐adrenoceptor coupled with site‐directed molecular docking and the target‐drug interaction by frontal analysis and injection amount–dependent method. Issue 7 (26th January 2017)

• Record Type: Journal Article
• Authors: Liu, Guangxin; Wang, Pei; Li, Chan; Wang, Jing; Sun, Zhenyu; Zhao, Xinfeng; Zheng, Xiaohui
• Is Part Of: Journal of molecular recognition. Volume 30:Issue 7(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-01-26
• Subjects: drug‐receptor interaction -- frontal analysis -- immobilized β2‐adrenoceptor -- protopine; Molecular recognition -- Periodicals; Models, Molecular -- Periodicals; Molecular Conformation -- Periodicals; Molecular Sequence Data -- Periodicals; Molecular Structure -- Periodicals; Carrier Proteins -- Periodicals; 572.8
• DOI: 10.1002/jmr.2613
• Languages: English
• ISSNs: 0952-3499

Abstract

Abstract: Drug‐protein interaction analysis is pregnant in designing new leads during drug discovery. We prepared the stationary phase containing immobilized β 2 ‐adrenoceptor ( β 2 ‐ AR) by linkage of the receptor on macroporous silica gel surface through N, N ′‐carbonyldiimidazole method. The stationary phase was applied in identifying antiasthmatic target of protopine guided by the prediction of site‐directed molecular docking. Subsequent application of immobilized β 2 ‐ AR in exploring the binding of protopine to the receptor was realized by frontal analysis and injection amount–dependent method. The association constants of protopine to β 2 ‐ AR by the 2 methods were (1.00 ± 0.06) × 10 5 M −1 and (1.52 ± 0.14) × 10 4 M −1 . The numbers of binding sites were (1.23 ± 0.07) × 10 −7 M and (9.09 ± 0.06) × 10 −7 M, respectively. These results indicated that β 2 ‐ AR is the specific target for therapeutic action of protopine in vivo. The target‐drug binding occurred on Ser 169 in crystal structure of the receptor. Compared with frontal analysis, injection amount–dependent method is advantageous to drug saving, improvement of sampling efficiency, and performing speed. It has grave potential in high‐throughput drug‐receptor interaction analysis. Abstract : β 2 ‐adrenoceptor was identified as the antiasthmatic target of protopine using receptor chromatography coupled with site‐directed molecular docking. Frontal analysis and injection amount‐dependent method were used for the binding interaction study.