Interactions Between N-Terminal Extracellular Tail of CCR4 and Natural Products of Licorice Using Capillary Electrophoresis
Interactions Between N-Terminal Extracellular Tail of CCR4 and Natural Products of Licorice Using Capillary Electrophoresis
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DOI：
10.1007/s10337-013-2474-y
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发表时间：
2013-05
期刊：
影响因子：
1.7
通讯作者：
Meina Li;Qing Wang;Xiaomei Ling;Lu Yang;Zhongjie Li;M. Ye;Ying Wang
中科院分区：
文献类型：
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作者：
Meina Li;Qing Wang;Xiaomei Ling;Lu Yang;Zhongjie Li;M. Ye;Ying Wang
甘草因其显著的生物抗炎活性而越来越受欢迎，而CC趋化因子受体4(CCR4)已被确定为治疗炎症性疾病的潜在重要药物靶点。首次建立了从甘草天然产物中筛选CCR4拮抗剂的毛细管电泳法。测定了甘草天然产物与CCR4 N端衍生的等效肽ML40的相互作用。结果表明，与阳性对照S009相比，有10个成分与ML40相互作用。结果表明，化合物与ML40的结合常数最大，为(3.636±0.2185)×104M−1。对CCL22/CCL17诱导的HEK293趋化有不同程度的抑制作用，表明与ML40结合较强的化合物具有CCR4拮抗作用。该方法可用于CCR4潜在拮抗剂的自动化高通量筛选。本研究为从甘草天然产物中开发抗炎化合物提供了潜在的理论基础。
Licorice is gaining popularity because of its significant biological anti-inflammatory activity, while CC chemokine receptor 4 (CCR4) has been identified as a potentially important drug target for the treatment of inflammatory diseases. Capillary electrophoresis was developed for screening for the first time of CCR4 antagonists from natural products of licorice. The interactions between natural products of licorice and ML40, the equivalent peptide derived from the N-terminal of CCR4, were determined. Twenty-eight ingredients were isolated and the results showed that ten of them interacted with ML40 compared with the positive control S009. The binding constants of the compounds to ML40 were calculated and the binding constant of liquiritin apioside (LA) was the largest among them (3.636 ± 0.2185) × 104M−1. The CCR4 antagonisms of the compounds that showed strong integration with ML40 were also confirmed by chemotaxis inhibition in which they displayed different degrees of inhibition to CCL22/CCL17-induced HEK293 chemotaxis. The methodology presented could be applied to automated high-throughput screening of potential antagonists of CCR4. This study provided the potential rationale for the development of anti-inflammatory compounds from natural products of licorice.