中文摘要：

本文利用荧光增敏光谱法及紫外吸收光谱法结合计算机模拟技术研究了模拟生理条件下文多灵碱的光谱特征及它与人血清白蛋白（human serum albumin,HSA）的键合作用。同步荧光及紫外光谱图的信息表明文多灵碱对蛋白微环境有影响。荧光光谱表明文多灵碱对HSA有较强的荧光增敏作用,根据荧光滴定的数据求得不同温度下（303、310和317K）药物与蛋白相互作用的结合常数及结合位点数。分子模拟的结果显示了文多灵碱与HSA的键合模式和键合机制,表明药物与蛋白有较强的键合作用,维持药物与蛋白的相互作用力主要是疏水作用,兼有4个氢键（位于氨基酸残基Arg218、Lys195、Arg222和Ala291位）。位点竞争实验显示文多灵碱键合在HSA的siteII区。通过计算得到的热力学参数（依据范德霍夫公式计算得ΔH0与ΔS0的值分别为-10.30kJ·mol^-1和79.98J·mol^-1·K-1）确定了药物与蛋白的相互作用力类型主要为疏水兼静电作用。

英文摘要：

In this paper,the fluorogenic property of vindoline was exploited and,as a probe,used to analyze the interaction of vindoline with HSA by fluorescence and absorption spectra in combination with molecular modeling under a simulated physiological conditions.The evidences from synchronous fluorescence and absorption spectroscopes showed the effect of vindoline on the microenvironment around HSA in aqueous solution.Data obtained by the fluorescence spectroscopy indicated that binding of vindoline with HSA leads to dramatic enhancement of the fluorescence emission intensity.The binding constants and the number of binding sites between vindoline and HSA at different temperatures （303,310 and 317 K） were calculated according to the data obtained from fluorescence titration.Molecular docking was performed to reveal the possible binding mode or mechanism and suggested that vindoline can bind strongly to HSA.It is considered that vindoline binds to HSA mainly by a hydrophobic interaction and there are four hydrogen bonds interactions between the drug and the residues Ala291,Arg222,Arg218 and Lys195,separately.Fluorescent displacement measurements confirmed that vindoline bind HSA on site II.The thermodynamic parameters obtained （the enthalpy change ΔH 0 and the entropy change ΔS 0 were calculated to be -10.30 kJ·mol ^-1 and 79.98 J·mol^-1·K^-1,respectively,according to the Van’t Hoff equation） suggested that hydrophobic and electrostatic interaction is the predominant intermolecular forces stabilizing the complex.