毛细管区带电泳研究化合物S009和CC趋化因子受体4三个胞外区相互作用

doi:10.5246/jcps.2014.03.025

中国药学(英文版)

毛细管区带电泳研究化合物S009和CC趋化因子受体4三个胞外区相互作用

杨璐, 帕子来提.亚库甫, 李美娜, 凌笑梅^*, 李中杰, 王应^*

1. 北京大学药学院天然药物及仿生药物国家重点实验室; 药物分析教研室, 北京 100191
2. 北京大学人类疾病基因研究中心; 北京大学医学部基础医学院免疫学系, 北京 100191

收稿日期:2013-11-09 修回日期:2013-12-01 出版日期:2014-03-13 发布日期:2013-12-23
通讯作者: *Corresponding author. Tel.: 86-10-82801590; 86-10-82802414; E-mail: lingxm@bjmu.edu.cn; yw@bjmu.edu.cn
作者简介:*Corresponding author. Tel.: 86-10-82801590; 86-10-82802414; E-mail: lingxm@bjmu.edu.cn; yw@bjmu.edu.cn
基金资助:
National Natural Science Foundation (Grant No. 81072612, 31270915 and 81071749), Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20110001110021 and 20120001110001) and the Open Foundation of State Key Laboratory of Natural and Biomimetic Drugs (Grant No. K20110109).

Study of the interactions between compound S009 and the extracellular loops of CC chemokine receptor 4 by capillary zone electrophoresis

Lu Yang, Pazilaiti Yakufu, Meina Li, Xiaomei Ling^*, Zhongjie Li, Ying Wang^*

1. State Key Laboratory of Natural and Biomimetic Drugs; Department of Pharmaceutical Analysis, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. Center for Human Disease Genomics; Department of Medical Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2013-11-09 Revised:2013-12-01 Online:2014-03-13 Published:2013-12-23
Contact: *Corresponding author. Tel.: 86-10-82801590; 86-10-82802414; E-mail: lingxm@bjmu.edu.cn; yw@bjmu.edu.cn
About author:*Corresponding author. Tel.: 86-10-82801590; 86-10-82802414; E-mail: lingxm@bjmu.edu.cn; yw@bjmu.edu.cn
Supported by:
National Natural Science Foundation (Grant No. 81072612, 31270915 and 81071749), Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20110001110021 and 20120001110001) and the Open Foundation of State Key Laboratory of Natural and Biomimetic Drugs (Grant No. K20110109).

摘要/Abstract

摘要：

CC趋化因子受体4 (CCR4) 是G蛋白偶联受体的一种, 在过敏性炎症中起着举足轻重的作用。在本研究中, 我们合成了CCR4的三个胞外loop区 (EL1–EL3), 用毛细管区带电泳 (CZE)的方法研究化合物S009和3个胞外loop区的相互作用。分别进行了定性和定量研究。实验数据表明, 化合物S009和EL3有相互作用并通过Scatchard方程计算得到化合物S009和EL3之间的结合常数为 (12.5±0.19)×10⁴M^–1。我们的研究确证了CCR4结合小分子的具体胞外域并为进一步发现新型CCR4拮抗剂提供了有帮助的信息。

关键词: CC趋化因子受体4, 毛细管区带电泳, 化合物 S009, ML40, 胞外loop区

Abstract:

CC chemokine receptor 4 (CCR4) is a G-protein-coupled receptor which plays a pivotal role in allergic inflammation. In the present study, three extracellular loops (EL1−3) of CCR4 were synthesized, and the interactions between the extracellular loops and compound S009 were investigated using capillary zone electrophoresis (CZE). Both qualitative and quantitative characterizations of the compound-peptide binding were carried out. The experimental data indicated that compound S009 exhibited interactions with EL3, and a binding constant of (12.5±0.19)×10⁴M^-1 was determined using the Scatchard plot. Our study identified the specific domains of CCR4 that could be targeted by small molecules and provided insights for the discovery of novel CCR4 antagonists.

Key words: CCR4, CZE, Compound S009, ML40, Extracellular loops

中图分类号:

R917

Supporting: National Natural Science Foundation (Grant No. 81072612, 31270915 and 81071749), Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20110001110021 and 20120001110001) and the Open Foundation of State Key Laboratory of Natural and Biomimetic Drugs (Grant No. K20110109).

杨璐, 帕子来提.亚库甫, 李美娜, 凌笑梅, 李中杰, 王应. 毛细管区带电泳研究化合物S009和CC趋化因子受体4三个胞外区相互作用[J]. 中国药学(英文版), DOI: 10.5246/jcps.2014.03.025.

Lu Yang, Pazilaiti Yakufu, Meina Li, Xiaomei Ling, Zhongjie Li, Ying Wang. Study of the interactions between compound S009 and the extracellular loops of CC chemokine receptor 4 by capillary zone electrophoresis[J]. Journal of Chinese Pharmaceutical Sciences, DOI: 10.5246/jcps.2014.03.025.

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毛细管区带电泳研究化合物S009和CC趋化因子受体4三个胞外区相互作用

Study of the interactions between compound S009 and the extracellular loops of CC chemokine receptor 4 by capillary zone electrophoresis

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