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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。
In this paper, the spectral characteristics of the radomutilide and its binding to human serum albumin (HSA) under simulated physiological conditions were studied by fluorescence-enhanced spectroscopy and ultraviolet absorption spectroscopy combined with computer simulation. Simultaneous fluorescence and UV spectroscopy information indicates that vinpocetine has an effect on the protein microenvironment. Fluorescence spectra showed that vinpocetine had a stronger fluorescence sensitizing effect on HSA. The binding constants and binding sites of drug-protein interaction at different temperatures (303, 310 and 317K) were obtained by fluorescence titration data. The results of molecular simulation showed that the bonding mode and bonding mechanism between vinorelbine and HSA showed that the drug and protein had a strong binding effect and that the interaction between drug and protein was mainly hydrophobic and combined with 4 Hydrogen bond (located at amino acid residues Arg218, Lys195, Arg222 and Ala291). Site competition experiments showed that vinorelbine binds to the site II region of HSA. The calculated thermodynamic parameters (values of ΔH0 and ΔS0 calculated according to the van der Hoff formula were -10.30 kJ · mol-1 and 79.98 J · mol-1 · K-1, respectively) confirmed the drug-protein interaction The main types of hydrophobic and electrostatic effects.