z-logo
Premium
Identifying the antiasthmatic target of doxofylline using immobilized β 2 ‐adrenoceptor based high‐performance affinity chromatography and site‐directed molecular docking
Author(s) -
Zhang Yajun,
Zeng Kaizhu,
Wang Jing,
Gao Haiyang,
Nan Yefei,
Zheng Xiaohui
Publication year - 2016
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.2549
Subject(s) - chemistry , docking (animal) , affinity chromatography , hydrogen bond , binding site , chromatography , molecular model , stereochemistry , enzyme , molecule , organic chemistry , biochemistry , medicine , nursing
As a xanthine derivative, doxofylline is believed to be dominant for fighting against asthma in practice. Unlike other xanthines, the antiasthmatic effects of doxofylline lack any definite proof of target and mediating mechanism according to previous reports. In this work, the interaction between doxofylline and β 2 ‐AR was investigated by high performance affinity chromatography using frontal analysis and nonlinear model. The methodology involved the immobilization of β 2 ‐AR on the silica gel by a random linking method, the determination of the binding parameters by frontal analysis and nonlinear chromatography and the exploration of the binding mechanism by site‐directed molecular docking. The association constant for doxofylline binding to immobilized β 2 ‐AR was determined to be 7.70 × 10 4  M −1 by nonlinear chromatography and 5.91 × 10 4  M −1 by frontal analysis. Ser 169 and Ser 173 were the binding sites for the receptor–drug interaction on which hydrogen bond was believed to be the main driven force during the interaction. These results indicated that the antiasthmatic effects of doxofylline may be behind the mediating mechanism of β 2 ‐AR. High performance affinity chromatography based on immobilized receptor has potential to become an alternative for drug target confirmation and drug–receptor interaction analysis. Copyright © 2016 John Wiley & Sons, Ltd.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here