1-(4-溴苯基)-5-苯基-1H-1,2,3-三氮唑键合人血清白蛋白的作用机制及抗菌活性  

Study on Interaction Mechanism of 1-(4-Bromophenyl)-5-phenyl-1H-1,2,3-triazole with Human Serum Albumin and Antibacterial Activity

作　　者：张宁[1] 岳玉林[1] 吴秀丽[1] 吴禄勇[1] 莫峥嵘[1] 司宏宗[2] 舒火明[3] 何文英[1] 

机构地区：[1]海南师范大学化学化工学院,海南海口571158 [2]青岛大学计算科学与工程技术研究中心,山东青岛266071 [3]海南经贸职业技术学院,海南海口571127

出　　处：《分析科学学报》2015年第6期757-762,共6页Journal of Analytical Science

基　　金：国家自然科学基金(No.21562019;21362008);海南省重点科技计划(No.ZDXM2014023);海南省自然科学基金(No.214031);海南省大学生创新训练项目(No.2013116580)

摘　　要：利用化学信息学、多种光谱法及抗菌实验,研究了1-(4-溴苯基)-5-苯基-1H-1,2,3-三唑(1-(4-bromophenyl)-5-phenyl-1H-1,2,3-triazole,BPTA)键合人血清白蛋白(HSA)的作用机制及抗菌活性。研究了BPTA的荧光光谱及紫外光谱;分子模拟确定了BPTA与HSA的键合区域和模式,位点竞争实验确定了BPTA在HSA亚结构域的位点Ⅱ发生作用。利用荧光偏振、紫外光谱、同步及三维荧光方法在模拟生理条件下研究了BPTA与HSA的作用机制及对蛋白微环境和二级结构的影响,并求得不同温度下BPTA与HSA作用的键合参数和热力学参数,确定了键合模式主要是疏水力作用、氢键及范德华作用。从分子水平上揭示了BPTA与HSA相互作用的机制,说明BPTA在生理条件下能被HSA载运至靶位发挥药效。另外,抗菌实验表明,BPTA对白色葡萄球菌、金黄色葡萄球菌、枯草芽孢杆菌、蜡状芽孢杆菌、四联球菌及白色念珠菌6种菌类均有明显的抑制作用。1-（4-Bromophenyl）-5-phenyl-1H-1,2,3-triazole（BPTA）was exploited to analyze its antibacterial activity and the binding to human serum albumin（HSA）by fluorescence polarization,synchronous fluorescence,3Dfluorescence spectra,and absorption spectra in combination with quantum chemistry and molecular modeling.Molecular docking was performed to reveal BPTA moiety bound to the hydrophobic cavity of HSA,and there were three hydrogen bonds between BPTA and the residues Arg117 and Arg186.Fluorescent displacement measurements confirmed that BPTA bound HSA on siteⅡ.The low anisotropy values suggested that BPTA molecules were bound in a motionally unrestricted environment introduced by HSA.The absorption,3Dand synchronous fluorescence spectroscopes of BPTA-HSA systems indicated that BPTA had an effect on the microenvironment around HSA in aqueous solution and quenched the intrinsic fluorescence of HSA.The binding parameters including the binding constants,the number of binding sites and average binding distance between BPTA and HSA at different temperatures indicated that BPTA could strongly bind HSA with one class of sites on HSA.The results from the thermodynamic parameters,molecular modeling and spectroscopy measurements suggested that the action forces of interactions were hydrophobic interaction,hydrogen bonding and vander wale force.In conclusion,the results revealed the binding mechanism of BPTA and HSA at the molecular level,indicating that BPTA can be carried to the target sites by HSA under physiological conditions.In addition,BPTA exhibited good inhibitory activities against Staphylococcus albus,Staphylococcus aureus,Bacillus subtilis,Bacillus cereus,Micrococcus tetragenus and Moniliaalbican.

关 键 词：1-(4-溴苯基)-5-苯基-1H-1 2 3-三唑 人血清白蛋白 分子模拟 光谱法 键合机制 

分 类 号：O657[理学—分析化学]