本文選題：結(jié)構(gòu)類似物　切入點：DNA　出處：《鄭州大學》2014年碩士論文　論文類型：學位論文

【摘要】：DNA通常是生物體遺傳信息的載體，同時也是大多數(shù)抗癌、抗病毒藥物的主要靶向分子，因此在生命科學的相關研究中對DNA的研究是極其重要的。藥物及其結(jié)構(gòu)類似物對DNA理化性質(zhì)的影響使DNA基因的復制和轉(zhuǎn)錄得到改變。因此對藥物及其結(jié)構(gòu)類似物與DNA的相互作用的研究不僅能探明致癌小分子或抗癌藥物與DNA相互作用的方式，還能為探究致癌及抗癌小分子的毒性、藥理及設計、合成新型相關的抗癌藥物小分子提供理論指導意義。 本文主要采用紫外可見光譜、熒光光譜和分子模擬等技術(shù)對小分子結(jié)構(gòu)類似物和fsDNA的相互作用等方面進行研究。主要包括以下部分：（1）綜述DNA和藥物小分子相互作用的研究現(xiàn)狀；（2）小分子結(jié)構(gòu)類似物與DNA相互作用的光譜法研究；（3）諾氟沙星和抗艾滋病新藥FNC相互作用的研究及其分析應用；（4）論文小結(jié)。 本文主要研究了大麻酚、Fluorazone系列、3-甲氧基-1，2-萘醌六種類似物等小分子化合物與fsDNA的相互作用。熒光光譜實驗表明它們均能使AO-DNA的熒光猝滅，為靜態(tài)猝滅，通過不同溫度下的雙對數(shù)方程和Van’t Hoff方程獲得了結(jié)合常數(shù)、結(jié)合位點、熱力學常數(shù)等數(shù)據(jù)，結(jié)果表明：大麻酚與DNA相互作用的主要作用力為疏水作用；SL-a與DNA相互作用的主要作用力為疏水作用和靜電結(jié)合，SL-b，SL-c，SL-d主要為氫鍵和范德華力；3-甲氧基-1，2-萘醌六種類似物等小分子化合物與DNA的相互作用中a，b，c，d，e，f均為疏水作用為主，b，c，e，f也存在靜電作用力；同時研究表明它們與DNA的結(jié)合模式均為嵌插結(jié)合，應用分子模擬技術(shù)來輔助說明與DNA結(jié)合的主要結(jié)合位點，結(jié)果顯示結(jié)合位點均為A-T豐富的堿基對間，，但插入的DNA序列位置有所不同。論文還研究了諾氟沙星和FNC的相互作用并應用于FNC含量的檢測，檢測的線性范圍：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).
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R96

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