【作者】 王珍；

【导师】 金璟；

【作者基本信息】 兰州大学 ， 有机化学， 2008， 硕士

【摘要】 小分子与生物大分子的相互作用研究已经成为化学、生命科学及临床药理学的重要研究内容。DNA和蛋白质是生物体中重要的生物大分子。临床上使用的许多抗癌、抗病毒药物都是以DNA为作用靶点,研究药物与DNA的相互作用,有助于从分子水平上了解抗癌、抗病毒药物的作用机理,为设计临床上更为有效的抗癌、抗病毒药物提供理论指导。蛋白质是药物的一种非常重要的运输载体。药物与蛋白质的相互作用不仅影响药物在体内的分布,而且还影响药物在体内的代谢与排泄方式,研究药物与蛋白质的结合为药物分子结构与药效之间的关系提供了有利的信息。基于研究生物大分子与小分子相互作用的的重要意义,本文采用荧光光谱、紫外可见吸收光谱和圆二色普研究了白杨素与人血清白蛋白的相互作用和葛根素与溶菌酶和DNA的相互作用。本论文共分为四部分:第一章:介绍了药物小分子与生物大分子相互作用的研究方法及研究现状。第二章:利用光谱学方法研究了白杨素与人血清白蛋白的相互作用,荧光光谱和CD谱表明由于白杨素的结合HSA的构象发生了变化,由CD数据计算了白杨素不存在和存在时HSA中α-螺旋结构的含量。此外,计算了反应的结合常数、结合位点数、热力学参数以及白杨素在HSA上的结合位置与色氨酸残基间的距离。第三章:应用荧光光谱和圆二色谱研究了葛根素与溶菌酶的相互作用。计算了不同温度下药物与溶菌酶相互作用的结合常数和结合位点数,根据热力学参数确定了作用力类型,并分析了药物对溶菌酶二级结构的影响。第四章:本章研究了模拟生理条件下葛根素与DNA的相互作用。利用紫外可见吸收光谱、荧光偏振方法和CD方法确定了葛根素与DNA的结合模式,根据荧光数据计算了反应的结合常数和结合位点数。更多还原

【Abstract】 The molecular interactions between molecule and biological molecular have become of an important research field in chemistry, life sciences and clinical medicine. DNA and proteins are key biological moleculars. DNA is the primary target molecular for most of anticancer and antivirus therapies. The investigation of the interaction of DNA with drugs is helpful to understand the mechanism by anticancer and antivirus medicines act and provide theoretical guidance for designing the effective drugs. Protein serves as a transport carrier for drugs, the binding of drugs with protein has a great influence not only upon the distribution of the drugs in the body but also upon their patterns of metabolism and excretion. The studies on this aspect may provide information of the structural features that determine the therapeutic effectiveness of drug. On the basis of the previous research, the fluorescence spectroscopy, UV-visible absorption spectroscopy and CD spectroscopy were used to investigate the interaction of drug with biological molecular.This paper consists of four sections as follows:Chapter 1: The methods and actuality about the research of the interaction between small molecular substances and biological molecular were summarized.Chapter 2: The binding of chrysin with HSA has been investigated by spectroscopy. The fluorescence and CD spectroscopy indicated that the conformation of HSA changed due to the binding of chrysin. Theα-helix contents of HSA in the absence and presence of chrysin were calculated by quantitative analysis of the CD spectra data. In addition, the binding constant, the number of binding sites, thermodynamic parameters and the distance between the binding location and tryptophan residue were calculated.Chapter 3: The interaction between puerarin and lysozyme has been studied using fluorescence and CD spectroscopy. The binding constant and the number of binding sites at three different temperature were calculated. The mainly intermolecular force induced by drugs binding was obtained according to the thermodynamic parameters. The effects of puerarin on Lysozyme secondary structure were investigated by CD spectroscopy.Chapter 4: This study was designed to examine the interaction between puerarin and DNA under simulated physiological conditions. The binding mode of puerarin and DNA was determined through UV-visible absorption spectroscopy, fluorescence polarization measurement and CD measurement. The binding constant and the number of binding sites were calculated from the data obtained from fluorescence experiments.更多还原