Screening of chemokine receptor CCR4 antagonists by capillary zone electrophoresis  

作　　者：Zhe Sun Lin-Jie Tian Qian Lin Xiao-Mei Ling Jun-Hai Xiao Ying Wang 

机构地区：[1]Department of Pharmaceutical Analysis of School of Pharmaceutical Sciences,and State Key Laboratory of Natural andBiomimetic Drugs,Peking University,Beijing 100191,PR China [2]Center for Human Disease Genomics,and Department of Medical Immunology of School of Basic Medical Science,Peking University,Beijing 100191,PR China [3]Beijing Institute of Pharmacology and Toxicology,Beijing 100850,PR China

出　　处：《Journal of Pharmaceutical Analysis》2011年第4期264-269,共6页药物分析学报(英文版)

基　　金：supported by the National Key New Drug Creation Program of China(2009ZX09103-724);the National Natural Science Foundation of China grants(30872292,90813025 and 81072612);the Natural Science Foundation of Beijing(7102107);the Open Foundation of State Key Laboratory of Natural and Biomimetic Drugs(K20090207);the National New Drug Research and Development Project of China(2009ZX09301-010)

摘　　要：CC chemokine receptor 4(CCR4)is a kind of G-protein-coupled receptor,which plays a pivotal role in allergic inflammation.The interaction between 2-(2-(4-chloro-phenyl)-5-{[(naphthalen-1-ylmethyl)-carbamlyl]-methyl-4-oxo-thiazolidin-3-yl)-N-(3-morpholin-4-yl-propyi)-acetamide(S009)and the N-terminal extracellular tail(ML40)of CCR4 has been validated to be high affinity by capillary zone electrophoresis(CZE).The S009 is a known CCR4 antagonist.Now,a series of new thiourea derivatives have been synthesized.Compared with positive control S009,they were screened using ML40 as target by CZE to find some new drugs for allergic inflammation diseases.The synthesized compounds XJH-5,XJH-4,XJH-17 and XJH-1 displayed the interaction with ML40,but XJH-9,XJH-10,XJH-I 1,XJH-12,XJH-13,XJH-14,XJH-3,XJH-8,XJH-6,XJH-7,XJH-15,XJH-16 and XJH-2 did not bind to ML40.Both qualification and quantification characterizations of the binding were determined.The affinity of the four compounds was valued by the binding constant,which was similar with the results of chemotactic experiments.The established CEZ method is capable of sensitive and fast screening for a series of lactam analogs in the drug discovery for allergic inflammation diseases.

关 键 词：Capillary zone electrophoresis CCR4 antagonist 2-(2-(4-chloro-phenyl)-5-{[(naphthalen-1-ylmethyl)-carbamoyl]-methyl}-4-oxo-thiazoli-din-3-yl)-N-(3-morpho-lin-4-yl-propyl)-aceta-mide Interactions Structural modification 

分 类 号：Q987[生物学—遗传学] Q78[生物学—人类学]