论文部分内容阅读
目的:表征2种呫吨酮类化合物(1-hydroxy-7-methoxyxanthone,HM;dehydrocycloguanandin,DC)与人血清白蛋白(human serum albumin,HSA)的键合作用。方法:在模拟生理条件下,应用计算机模拟技术,并结合荧光光谱法和紫外吸收光谱法研究药物与蛋白的相互作用。结果:分子模拟显示了DC及HM与HSA的键合区域和键合模式,表明维持药物与蛋白质的相互作用力主要是疏水作用,兼有位于不同氨基酸残基的氢键。荧光光谱实验结果表明:这2种呫吨酮类化合物对HSA的荧光在一定的浓度范围内都有猝灭作用,猝灭方式均为静态猝灭。紫外光谱图表明它们对蛋白微环境有影响。根据荧光滴定数据,求出了不同温度下(296,303,310 K)反应的结合常数及反应热力学参数。通过竞争实验确定了这2种药物在蛋白上的不同结合位点。结论:在分子水平上揭示了这2种呫吨酮类化合物与HSA有不同的、较强的键合作用。
OBJECTIVE: To characterize the binding of two kinds of 1-hydroxy-7-methoxyxanthone (HM) to human serum albumin (HSA). Methods: Under simulated physiological conditions, the interaction between drugs and proteins was studied by computer simulation and fluorescence spectroscopy and ultraviolet absorption spectroscopy. Results: Molecular simulation showed the binding domains and bonding modes of DC, HM and HSA, indicating that the interaction between drug and protein was mainly hydrophobic and that there were hydrogen bonds between different amino acid residues. Fluorescence spectra experiment results show that these two xanthone compounds quench the fluorescence of HSA in a certain concentration range, and the quenching methods are all static quenching. UV spectroscopy shows that they have an effect on the protein microenvironment. According to the fluorescence titration data, the binding constants and reaction thermodynamic parameters of the reaction at different temperatures (296,303,310 K) were obtained. The different binding sites of the two drugs on the protein were determined by competitive experiments. Conclusion: The two kinds of xanthone compounds have different and stronger bonding effects with HSA at the molecular level.