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

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（英文）

作　　者：杨璐[1,2] 帕子来提.亚库甫 李美娜[1,2] 凌笑梅[1,2] 李中杰[1,2] 王应[3,4] 

机构地区：[1]北京大学药学院天然药物及仿生药物国家重点实验室 [2]药物分析教研室,北京100191 [3]北京大学人类疾病基因研究中心 [4]北京大学医学部基础医学院免疫学系,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》2014年第3期186-189,共4页中国药学（英文版）

基　　金：National Natural Science Foundation(Grant No.81072612,31270915 and 81071749);Specialized Research Fund for the Doctoral Program of Higher Education of China(Grant No.201 10001110021 and 20120001110001);the Open Foundation of State Key Laboratory of Natural and Biomimetic Drugs(Grant No.K20110109)

摘　　要：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）×10^4 M^-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.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)×104 M–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：CCR4 CZE Compound S009 ML40 Extracellular loops 

分 类 号：R914[医药卫生—药物化学]