光谱和分子模拟法研究核酸与小分子及结构类似物的相互作用

发布时间：2018-03-07 23:04

本文选题：结构类似物　切入点：DNA　出处：《郑州大学》2014年硕士论文　论文类型：学位论文

【摘要】：DNA通常是生物体遗传信息的载体，同时也是大多数抗癌、抗病毒药物的主要靶向分子，因此在生命科学的相关研究中对DNA的研究是极其重要的。药物及其结构类似物对DNA理化性质的影响使DNA基因的复制和转录得到改变。因此对药物及其结构类似物与DNA的相互作用的研究不仅能探明致癌小分子或抗癌药物与DNA相互作用的方式，还能为探究致癌及抗癌小分子的毒性、药理及设计、合成新型相关的抗癌药物小分子提供理论指导意义。本文主要采用紫外可见光谱、荧光光谱和分子模拟等技术对小分子结构类似物和fsDNA的相互作用等方面进行研究。主要包括以下部分：（1）综述DNA和药物小分子相互作用的研究现状；（2）小分子结构类似物与DNA相互作用的光谱法研究；（3）诺氟沙星和抗艾滋病新药FNC相互作用的研究及其分析应用；（4）论文小结。本文主要研究了大麻酚、Fluorazone系列、3-甲氧基-1，2-萘醌六种类似物等小分子化合物与fsDNA的相互作用。荧光光谱实验表明它们均能使AO-DNA的荧光猝灭，为静态猝灭，通过不同温度下的双对数方程和Van’t Hoff方程获得了结合常数、结合位点、热力学常数等数据，结果表明：大麻酚与DNA相互作用的主要作用力为疏水作用；SL-a与DNA相互作用的主要作用力为疏水作用和静电结合，SL-b，SL-c，SL-d主要为氢键和范德华力；3-甲氧基-1，2-萘醌六种类似物等小分子化合物与DNA的相互作用中a，b，c，d，e，f均为疏水作用为主，b，c，e，f也存在静电作用力；同时研究表明它们与DNA的结合模式均为嵌插结合，应用分子模拟技术来辅助说明与DNA结合的主要结合位点，结果显示结合位点均为A-T丰富的碱基对间，，但插入的DNA序列位置有所不同。论文还研究了诺氟沙星和FNC的相互作用并应用于FNC含量的检测，检测的线性范围：1.29~36.20μg·mL-1。
[Abstract]:DNA is usually the carrier of genetic information in organisms, and it is also the main target molecule of most anticancer and antiviral drugs. Therefore, the study of DNA in the life sciences is extremely important. The effects of drugs and their structural analogues on the physical and chemical properties of DNA alter the replication and transcription of DNA gene. The study of interaction with DNA can not only identify the way in which small carcinogenic molecules or anticancer drugs interact with DNA, It can also provide theoretical guidance for exploring the toxicity, pharmacology and design of carcinogenic and anticancer small molecules and synthesizing new anticancer drugs. In this paper, we mainly use UV-Vis spectrum. Fluorescence spectroscopy and molecular simulation techniques were used to study the interaction between small molecular structural analogues and fsDNA. The main contents are as follows: 1) A review of the research status of DNA and drug small molecule interaction. Spectroscopic study on the interaction between substance and DNA 3) the study on the interaction between norfloxacin and new anti-AIDS drug FNC and its analysis and application are summarized in this paper. In this paper, the interaction between six small molecular compounds of cannabinol Fluorazone series (3-methoxy-1-methoxy-2-naphthoquinone) and fsDNA has been studied. The fluorescence spectra show that they can quench the fluorescence of AO-DNA and become static quenching. The data of binding constant, binding site, thermodynamic constant and so on were obtained by using double logarithmic equation and Van't Hoff equation at different temperatures. The results show that the main interaction force between cannabinol and DNA is hydrophobic. The main interaction force between SL-a and DNA is hydrophobic and electrostatic binding SL-bSL-SL-SL-d is mainly composed of hydrogen bond and van der Waals 3-methoxy-1-methoxy-2-naphthoquinone. In the interaction between DNA and other small molecular compounds, the hydrophobic action is the main factor, and there is also electrostatic interaction. At the same time, it was found that the binding patterns of DNA were intercalated and intercalated. Molecular simulation was used to explain the main binding sites to DNA. The results showed that the binding sites were A-T rich base pairs. However, the position of inserted DNA sequence was different. The interaction between norfloxacin and FNC was also studied and applied to the detection of FNC content. The linear range of detection was in the range of: 1.29 ~ 36.20 渭 g 路ml ~ (-1).
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R96

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