多光谱法与分子对接模型研究西维来司钠与弹性蛋白酶的相互作用  

Interaction Between Sivelestat Sodium and Elastase by Multispectra and Molecular Docking

作　　者：尹广婷 周雪健 姚红柳 付金凤 曹洪玉[2] 郑学仿[2] 苏丽红 YIN Guang-Ting;ZHOU Xue-Jian;YAO Hong-Liu;FU Jin-Feng;CAO Hong-Yu;ZHENG Xue-Fang;SU Li-Hong(College of Chemistry,Changchun Normal University,Changchun 130032,China;S chool of Life Science and Technology,Dalian University,Dalian 116622,China)

机构地区：[1]长春师范大学化学学院,长春130032 [2]大连大学生命科学与技术学院,大连116622

出　　处：《应用化学》2022年第6期960-968,共9页Chinese Journal of Applied Chemistry

基　　金：吉林省科技厅项目(No.20140101043JC);吉林省教育厅项目(吉教科合字[2013]第251号);长春师范大学自然科学基金项目(长师大自科合字[2018]第016号)资助。

摘　　要：采用多种光谱法及分子对接技术对西维来司钠(ONO-5046)与弹性蛋白酶的相互作用进行研究,利用荧光光谱法判断出ONO-5046的加入对弹性蛋白酶产生荧光猝灭作用,与弹性蛋白酶相互作用的猝灭类型为静态猝灭,ONO-5046与弹性蛋白酶以结合比为1∶1的比例构成复合物。经计算,ONO-5046与弹性蛋白酶体系的ΔH<0和ΔS<0,判断出氢键与范德华力为其主要结合作用力,由ΔG<0可知该反应可以自发进行。同步荧光光谱法、紫外-可见分光光谱法和圆二色光谱法探讨了ONO-5046的加入使弹性蛋白酶中氨基酸残基周围环境的疏水性降低,二级结构发生改变,α-螺旋结构的比例减少,无规则卷曲的比例增多;分子对接模拟结果表明:在与弹性蛋白酶相互作用过程中,ONO-5046分子骨架上的多个酰基结构、2个苯环以及较长的共轭结构能提供氢键与范德华力的作用位点,同时,端碳上的3个甲基结构有利于疏水作用,ONO-5046上的氧负离子与弹性蛋白酶的精氨酸存在盐桥作用。以上结果表明,ONO-5046与弹性蛋白酶的结合存在多种作用力,能形成稳定的复合物,从而抑制了弹性蛋白酶的活性。The interaction of sivelestat sodium(ONO-5046)and elastase was investigated using multispectral and molecular docking method. The fluorescence spectrum of the elastase is quenched by ONO-5046 and the mechanism of action is a static quenching process. ONO-5046 can bind with elastase to form 1∶1 complex.The thermodynamic parameters are calculated to be ΔH < 0,ΔS < 0. Thermodynamic analysis suggests that hydrogen bonds and van der Waal′s forces are the main forces between ONO-5046 and elastase. ΔG<0suggests that the interaction is a spontaneous process. The synchronous fluorescence spectrum,UV-Vis absorption and the circular dichroism spectra results show that the hydrophobicity of the environment around the amino acid residues in elastase decreases,the formation of ONO-5046 complex can influence some conformation changes of elastase,the proportion of α-helix structure decreases,the proportion of irregular crimp increases. The molecular docking simulation technique displays that a plurality of acyl structures,benzene rings and conjugated structures in the molecular skeleton of ONO-5046 provide the action site of the hydrogen bond and van der waals force,the three methyl groups on the end carbon are favorable for hydrophobicity,the electrolytic bridge is between oxygen anion and arignine of PPE. The results suggest that multiple forces exist between ONO-5046 and elastase system to form a stable compound,which inhibits the overexpression of elastase.

关 键 词：西维来司钠 弹性蛋白酶 多光谱法 分子对接技术 

分 类 号：O656[理学—分析化学]