黄酮类化合物与DNA及其组成碱基的相互作用研究

发布时间：2018-04-25 09:30

本文选题：黄酮类化合物 + 小牛胸腺DNA　；参考：《浙江大学》2005年硕士论文

【摘要】：脱氧核糖核酸(DNA)是基本的生命物质,对一切生命现象都起着至关重要的作用。在分子水平上阐明这些生物大分子与小分子、离子,特别是药物分子的相互作用是当前生命科学、临床医学、药物化学及化学等众多领域的重要研究课题。本论文主要研究了脱氧核糖核酸(DNA)及其组成碱基与黄酮类化合物的相互作用,其主要内容由四个部分组成。论文第一部分介绍了黄酮类化合物的结构、性质和生理活性,然后阐述了近年来在生物大分子DNA与分子相互作用研究领域的研究进展情况,归纳了生物大分子DNA与小分子相互作用的方式及特点,总结了研究它们相互作用的所采用的各种方法及仪器,说明了该研究对生物、医学及化学上的重要意义。第二部分我们在LKB—2275型生物活性检测仪上采用等温滴定微量热法(ITC)在298.15K条件下研究了DNA组成碱基腺嘌呤、嘌呤、鸟嘌呤、嘧啶和胞嘧啶等主体分子与11种黄酮类化合物的相互作用,得到了它们相互作用的结合位点数、结合常数等维合参数和相互作用焓变、相互作用Gibbs自由能变化和相互作用熵变等热力学参数。发现嘧啶、腺嘌呤、鸟嘌呤和胞嘧啶等DNA碱基在与黄酮类化合物发生相互作用的时候,存在明显差别,即在与不同作用对象作用时,这些DNA碱基的作用位点不同。通过分析这些相互作用的数据,得到黄酮类化合物与腺嘌呤、嘌呤发生相互作用时,腺嘌呤上9位的氮原子、鸟嘌呤上9位的氮原子和6位上的羰基,胞嘧啶中1位氮原子和2位羰基结构是主要作用位点。研究中发现,由于空间位阻效应,含有较多羟基数目的黄酮类化合物,如槲皮素、木樨草素、杨梅黄酮、芦丁与腺嘌呤的之间的芳香氢键作用大大降低,但是这些黄酮类化合物却由于B环羟基与胞嘧啶和鸟嘌呤上的羰基形成分子间氢键,从而相互作用加强,表现出较高的摩尔反应焓。此外我们也应用了紫外可见光谱法研究了腺嘌呤、鸟嘌呤、嘧啶、胞嘧啶等主体分子与黄酮类化合物的相互作用。发现嘧啶的加入使黄酮的吸收峰没有发生变化,而腺嘌呤、鸟嘌呤和胞嘧啶的加入,使黄酮的吸收峰发生明显变化,说明了DNA碱基分子通过N原子上的氢原子与黄酮类化合物发生作用。同时我们也看到腺嘌呤和嘧啶与槲皮素作用后,槲皮素的吸收峰没有发生峰移,而胞嘧啶和鸟嘌呤的加入,使槲皮素两处吸收峰发生明显变化。比较槲皮素和桑色素分别与
[Abstract]:Deoxyribonucleic acid (DNA) is a basic living substance, which plays an important role in all life phenomena. To clarify the interaction of these biological macromolecules with small molecules, ions, especially drug molecules at the molecular level is an important research topic in many fields such as life science, clinical medicine, drug chemistry and chemistry. In this paper, the interaction of DNA and its constituent bases with flavonoids is studied. The main contents are composed of four parts. In the first part of this paper, the structure, properties and physiological activity of flavonoids are introduced, and the progress in the field of interaction between DNA and molecular is reviewed. The ways and characteristics of interaction between biological macromolecules DNA and small molecules are summarized. Various methods and instruments used to study the interaction between DNA and small molecules are summarized. The significance of this study to biology, medicine and chemistry is explained. In the second part, we studied the composition of basic adenine, purine, guanine by isothermal titration microcalorimetry at 298.15K on LKB-2275 bioactivity detector. The interaction of pyrimidine and cytosine with 11 flavonoids, the binding sites, the binding constants and the enthalpy of interaction are obtained. The thermodynamic parameters such as the variation of the free energy of interaction Gibbs and the change of entropy of interaction are discussed. It was found that DNA bases such as pyrimidine, adenine, guanine and cytosine have obvious differences when interacting with flavonoids, that is, when interacting with different objects, these DNA bases have different action sites. By analyzing the data of these interactions, we found that when flavonoids interact with adenine and purine, nine nitrogen atoms in adenine, nine nitrogen atoms in guanine and six carbonyl groups in guanine. In cytosine, one nitrogen atom and two carbonyl structures are the main sites. It was found that the aromatic hydrogen bond between quercetin, luteolin, myricetin, rutin and adenine was greatly reduced due to the steric steric effect of flavonoids containing more hydroxyl groups, such as quercetin, luteolin, myricetin, rutin and adenine. However, these flavonoids form intermolecular hydrogen bonds with the carbonyl groups on cytosine and guanine, thus the interaction is strengthened and the molar reaction enthalpy is high. In addition, the interaction between adenine, guanine, pyrimidine, cytosine and flavonoids was studied by UV-Vis spectroscopy. It was found that addition of pyrimidine did not change the absorption peak of flavonoids, while adenine, guanine and cytosine increased the absorption peak of flavonoids. It is shown that DNA bases interact with flavonoids by hydrogen atoms on N atoms. At the same time, we also see that the absorption peak of quercetin does not shift after the action of adenine and pyrimidine with quercetin, but the addition of cytosine and guanine makes the absorption peak of quercetin change obviously. Comparison of quercetin and mulberry pigment
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：Q523

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