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高等学校化学研究 ›› 2004, Vol. 20 ›› Issue (6): 738-742.

• Articles • 上一篇    下一篇

A High-affinity Activator of G551D-CFTR Chloride Channel Identified By High Throughput Screening

ZHAO Lu1,3, HE Cheng-yan2, LIU Yan-li1, ZHOU Hong-lan2, ZHOU Jin-song2, SHANG De-jing4, YANG Hong4   

  1. 1. Membrane Channel Research Laboratory, Northeast Normal University, Changchun 130024, P. R. China;
    2. China-Japan Union Hospital, Jilin University, Changchun 130033, P. R. China;
    3. College of Traditional Chinese Medicine Material, Jilin Agricultural University, Changchun 130118, P. R. China;
    4. Faculty of Life Sciences, Liaoning Normal University, Dalian 116029, P. R. China
  • 收稿日期:2004-03-19 出版日期:2004-12-24 发布日期:2011-08-06
  • 基金资助:

    Supported by the Start-up Fund for Returned Overseas Scholars from Northeast Normal University, National Science Fund for Distinguished Young Scholars(No.30325011), Distinguished Young Scholars Fund of Jilin Province(No.20030112), Excellent Young Teachers Program of MOE, P. R. China and the National Science Foundation of Jilin Province(No.20010548 and 20030708).

A High-affinity Activator of G551D-CFTR Chloride Channel Identified By High Throughput Screening

ZHAO Lu1,3, HE Cheng-yan2, LIU Yan-li1, ZHOU Hong-lan2, ZHOU Jin-song2, SHANG De-jing4, YANG Hong4   

  1. 1. Membrane Channel Research Laboratory, Northeast Normal University, Changchun 130024, P. R. China;
    2. China-Japan Union Hospital, Jilin University, Changchun 130033, P. R. China;
    3. College of Traditional Chinese Medicine Material, Jilin Agricultural University, Changchun 130118, P. R. China;
    4. Faculty of Life Sciences, Liaoning Normal University, Dalian 116029, P. R. China
  • Received:2004-03-19 Online:2004-12-24 Published:2011-08-06
  • Supported by:

    Supported by the Start-up Fund for Returned Overseas Scholars from Northeast Normal University, National Science Fund for Distinguished Young Scholars(No.30325011), Distinguished Young Scholars Fund of Jilin Province(No.20030112), Excellent Young Teachers Program of MOE, P. R. China and the National Science Foundation of Jilin Province(No.20010548 and 20030708).

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被引次数

9

摘要： A stably transfected CHO cell line coexpressing G551D-CFTR and iodide-sensitive yellow fluorescent protein mutant EYFP-H148Q-I152L was successfully established and used as assay model to identify small-molecule activators of G551D-CFTR chloride channel from 100000 diverse combinatorial compounds by high throughput screening on a customized Beckman robotic system. A bicyclooctane compound was identified to activate G551D-CFTR chloride channel with high-affinity(Kd=1.8 μmol/L). The activity of the bicyclooctane compound is G551D-CFTR-specific, reversible and non-toxic. The G551D-CFTR activator may be useful as a tool to study the mutant G551D-CFTR chloride channel structure and transport properties and as a candidate drug to cure cystic fibrosis caused by G551D-CFTR mutation.

关键词: Cystic fibrosis, Yellow fluorescent protein(YFP), High throughput screening(HTS), Small molecule

Abstract: A stably transfected CHO cell line coexpressing G551D-CFTR and iodide-sensitive yellow fluorescent protein mutant EYFP-H148Q-I152L was successfully established and used as assay model to identify small-molecule activators of G551D-CFTR chloride channel from 100000 diverse combinatorial compounds by high throughput screening on a customized Beckman robotic system. A bicyclooctane compound was identified to activate G551D-CFTR chloride channel with high-affinity(Kd=1.8 μmol/L). The activity of the bicyclooctane compound is G551D-CFTR-specific, reversible and non-toxic. The G551D-CFTR activator may be useful as a tool to study the mutant G551D-CFTR chloride channel structure and transport properties and as a candidate drug to cure cystic fibrosis caused by G551D-CFTR mutation.

Key words: Cystic fibrosis, Yellow fluorescent protein(YFP), High throughput screening(HTS), Small molecule