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-1ylmethyl)-carbamoyl]-methyl}-4-oxo-thiazolidin-3-yl)-N-(3-morpholin-4-yl-propyl)-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-11,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.
Zhe SunLin-Jie TianQian LinXiao-Mei LingJun-Hai XiaoYing Wang
建立快速简便的在线固相萃取液相(on-line SPE HPLC-DAD)分析方法,测定大鼠血浆中环磷酰胺的浓度。该方法为:将Acclaim Polar Advantage II C18保护柱(PA II柱,10mm×4.6mm,5μm)作为在线SPE柱,去蛋白的血浆样品进样后,100%H2O洗脱1min;经PA II C18柱(150mm×4.6mm,5μm)分析,流动相为乙腈水(40:60,v/v),流速为1mL/min,检测波长为195nm。经过验证发现该方法的选择性好,线性、精密度、准确度和灵敏度高,可用于临床监测环磷酰胺浓度。
