作　　者： ; ; ; ; ;

机构地区： 广西科技大学生物与化学工程学院

出　　处： 《生物技术通讯》 2012年第4期527-531,共5页

摘　　要： 目的:研究抗5-脂氧合酶酚类抑制剂的结构活性关系及作用机制。方法:构建7个抗5-脂氧合酶阳性酚类抑制剂分子库,利用Autodock 4.2和iGEMDOCK 2.1软件包对受体与抑制剂进行模拟对接研究并计算结合自由能。结果:用Autodock 4.2、iGEMDOCK 2.1计算得到的结合自由能与抑制剂的抑制活性之间都存在良好的相关性,它们的决定系数(R2)依次为0.856 64和0.784 41,标准误差(SD)分别为0.430 92和5.323 35,P值分别为0.002 79和0.007 98;配体与受体之间形成的氢键在决定配体在受体活性部位的构象及定位中起重要作用,但两者结合的主要驱动力为范德华作用力;具有碳氧双键及与该双键共轭的碳碳双键的多环酚类化合物有较强的抗5-脂氧合酶活性。结论:Autodock 4.2比iGEMDOCK 2.1预测抗5-脂氧合酶酚类抑制剂的能力强;具有碳氧双键及与该双键共轭的碳碳双键的多环酚类化合物有较强的抗5-脂氧合酶活性。 Objective： To study the structure-activity relationships of phenolic inhibitor against 5-1ipoxygenase and the mechanism of their interaction. Methods： Seven positive phenolic inhibitors against 5-1ipoxygenase were collected and constructed, the inhihitors were docked into the acitve site of 5-1ipoxygenase and the binding free energy was calculated by using both Autodock 4.2 and iGEMDOCK 2.1. Results： A good linear correlation existed between the binding free energy calculated by using both Autodoek 4.2 and iGEMDOCK 2.1 and the correspond- ing inhibitory activity, for the values of the coefficient of determination（R2） were 0.856 64 and 0.784 41, respectively, SD were 0.430 92 and 5.323 35, and P values were 0.002 79 and 0.007 98 respectively. The hydrogen bonds formed between the ligand and receptor active site played a vital role in determining the ligand conformation and orient located in the active site of the receptor, but the main driving force in the binding of small molecular inhibitor to 5-1ipoxygenase active site was van der Waals force. The polycyclic phenolic compound with carbonyl group conjugated with a carbon carbon double bond had high potent inhibitory activity against 5-1ipoxygenase. Conclusion： The predictive ability of phenoie inhibitors against 5-1ipoxygenase by using Autodock 4.2 was typically stronger than that by using iGEMDOCK 2.1. The polycyclic phenolic compound with carbonyl group conjugated with a carbon carbon double bond had high potent inhibitory activity against 5-1ipoxygenase.

关 键 词： 脂氧合酶 酚类抑制剂 抗炎 分子对接 结构活性关系

领　　域： [生物学] [理学] [理学]