本文關(guān)鍵詞：光譜及分子對接技術(shù)研究小分子藥物與DNA、蛋白的相互作用　出處：《長春師范大學》2017年碩士論文　論文類型：學位論文

  更多相關(guān)文章： 藥物 血清白蛋白 DNA 光譜法 分子對接

【摘要】：本文主要采用光譜法和分子對接法研究了幾種小分子藥物與血清白蛋白和DNA的相互作用,主要研究內(nèi)容如下:在pH=7.40的條件下,采用多種光譜技術(shù)研究了隱丹參酮與人血清白蛋白(HSA)的相互作用。隱丹參酮對HSA的猝滅過程為靜態(tài)猝滅,并獲得了在不同溫度下隱丹參酮與HSA作用的結(jié)合常數(shù)和結(jié)合位點數(shù)。熱力學參數(shù)研究發(fā)現(xiàn)隱丹參酮與HSA的主要結(jié)合力為靜電作用力。位點競爭實驗結(jié)果表明隱丹參酮結(jié)合在HSA的site I位。同步熒光光譜法和圓二色光譜法的結(jié)果表明隱丹參酮的加入使HSA的二級結(jié)構(gòu)發(fā)生變化�？疾炝私饘匐x子對隱丹參酮-HSA體系的影響。根據(jù)F?rster理論,計算得到隱丹參酮與HSA之間的結(jié)合距離r0為2.86 nm。利用光譜法和分子對接法研究了昔萘酸沙美特羅與牛血清白蛋白(BSA)的相互作用。紫外光譜法表明BSA的加入對昔萘酸沙美特羅的紫外吸收光譜產(chǎn)生影響。熒光猝滅和時間分辨熒光光譜法的結(jié)果表明昔萘酸沙美特羅對BSA的猝滅過程為靜態(tài)猝滅。得到了不同溫度下的結(jié)合常數(shù)和結(jié)合位點數(shù),結(jié)合作用力為靜電作用。位點競爭實驗和分子對接法的結(jié)果顯示昔萘酸沙美特羅結(jié)合在BSA的site I位。紅外光譜法、同步熒光光譜法和圓二色光譜法的結(jié)果表明昔萘酸沙美特羅的加入對BSA的二級結(jié)構(gòu)產(chǎn)生影響。此外,還探究了K+、Ca2+、Cu2+、Zn2+和Fe3+對昔萘酸沙美特羅-BSA體系的影響。計算得到昔萘酸沙美特羅與BSA之間的結(jié)合距離為2.37 nm。采用光譜法、粘度法、電化學法和分子對接法研究氫溴酸右美沙芬與DNA的相互作用。熒光猝滅和時間分辨熒光光譜法的結(jié)果表明二者的猝滅過程為靜態(tài)猝滅。獲得了291、301和311 K下的結(jié)合常數(shù)和結(jié)合位點數(shù),熱力學參數(shù)的結(jié)果表明氫溴酸右美沙芬與DNA以范德華力或氫鍵相結(jié)合,結(jié)合距離為2.54 nm。紅外光譜法和圓二色光譜法的結(jié)果表明氫溴酸右美沙芬的加入對DNA的二級結(jié)構(gòu)產(chǎn)生了影響。紫外吸收光譜法、離子強度實驗、粘度法、熔解溫度實驗和與單鏈DNA(ssDNA)作用的結(jié)果均表明氫溴酸右美沙芬與DNA的結(jié)合是嵌插作用。分子對接的結(jié)果表明二者以嵌插模式相結(jié)合,在結(jié)合的過程中,氫鍵發(fā)揮了重要作用。循環(huán)伏安法和微分脈沖伏安法的結(jié)果顯示DNA的加入使氫溴酸右美沙芬的峰電位發(fā)生了移動。以吖啶橙(AO)為探針研究了硫酸新霉素和硫酸巴龍霉素與DNA的相互作用。熒光猝滅法和時間分辨熒光光譜法的結(jié)果表明硫酸新霉素/硫酸巴龍霉素與AO-DNA的作用是靜態(tài)猝滅過程。在291 K時,硫酸新霉素和硫酸巴龍霉素與AO-DNA的結(jié)合常數(shù)分別為6.70×103和1.44×103 L·mol-1。ΔH、ΔS和ΔG的結(jié)果表明硫酸新霉素/硫酸巴龍霉素與AO-DNA以范德華力和氫鍵發(fā)生結(jié)合。紅外光譜法和圓二色光譜法的結(jié)果表明硫酸新霉素/硫酸巴龍霉素的加入對DNA的二級結(jié)構(gòu)產(chǎn)生了影響。離子強度實驗、粘度法、熔解溫度實驗和與ssDNA作用的實驗結(jié)果均證明硫酸新霉素/硫酸巴龍霉素與DNA以溝區(qū)模式相結(jié)合。分子對接法進一步表明硫酸新霉素/硫酸巴龍霉素結(jié)合在DNA小溝區(qū)的A-T富裕區(qū)。采用光譜法、粘度法和分子對接法研究了以溴化乙錠(EB)為熒光探針小諾霉素/妥布霉素與DNA的相互作用。熒光猝滅法和時間分辨熒光光譜法的結(jié)果表明小諾霉素/妥布霉素與EB-DNA的作用是靜態(tài)猝滅過程。得到了不同溫度下小諾霉素/妥布霉素與EB-DNA的結(jié)合常數(shù)和結(jié)合位點數(shù),ΔH、ΔS和ΔG的結(jié)果表明小諾霉素/妥布霉素與EB-DNA以范德華力和氫鍵發(fā)生結(jié)合。紅外光譜法和圓二色光譜法表明小諾霉素/妥布霉素的加入對DNA的二級結(jié)構(gòu)產(chǎn)生了影響。離子強度實驗、粘度法、熔解溫度實驗和單雙鏈DNA對比實驗的結(jié)果均表明小諾霉素/妥布霉素與DNA的作用模式為溝區(qū)結(jié)合。分子對接法表明小諾霉素/妥布霉素與DNA以溝區(qū)模式相結(jié)合,在結(jié)合過程中氫鍵發(fā)揮了重要作用。
[Abstract]:This paper mainly uses the interaction of spectroscopy and molecular docking method of several small molecule drugs and serum albumin and DNA, the main research contents are as follows: under the condition of pH=7.40 of cryptotanshinone and human serum albumin (HSA) using a variety of spectroscopic techniques. The interactions of cryptotanshinone on quenching process for HSA static quenching, and the binding constants obtained at different temperatures of cryptotanshinone and HSA and the number of binding sites. The study found the main thermodynamic parameters of the binding force of cryptotanshinone and HSA electrostatic interaction. Experimental results show that the site competition with Cryptotanshinone in HSA site I. Synchronous fluorescence spectroscopy and circular two color spectroscopy results showed cryptotanshinone with two level structure makes the change of HSA. The effects of metal ions on the cryptotanshinone -HSA system. According to the F? Rster theory, calculation of cryptotanshinone With the combination of HSA and the distance between the R0 is studied with naphthalene Shah Mette Lo acid and bovine serum albumin in 2.86 nm. by spectroscopy and molecular docking method (BSA). The interactions of UV spectra showed that the addition of BSA on UV in naphthalene acid Shah Mette Lo had influenced the absorption spectra. The fluorescence quenching and time-resolved fluorescence spectroscopy the results show that with naphthalene acid Shah Mette Lo BSA quenching is static quenching. The binding constants and binding sites under different temperatures, binding force is electrostatic interaction. The results of site competition experiments and molecular docking method show that with naphthalene acid sand Emmett combination in BSA site, I. Infrared spectroscopy, synchronous fluorescence round two color spectroscopy and spectrometry results show that with naphthalene acid Shah Mette Lo joined the two stage structure influence BSA. In addition, it also explores the K+, Ca2+, Cu2+, Zn2+ and Fe3+ in Shah Mette Lo -BSA of naphthalene acid The effects obtained. Combined with the distance of 2.37 nm. by spectroscopy, viscosity method between naphthalene acid and BSA in Shah Mette Lo, the interaction of electrochemical method and molecular docking method of Dextromethorphan Hydrobromide and DNA. Fluorescence quenching and time-resolved fluorescence spectroscopy results show that the quenching process of the two is a static quenching procedure. The binding constants and binding sites of 291301 and 311 K, the results show that the thermodynamic parameters of Dextromethorphan Hydrobromide combined with DNA by Fan Dehua force or hydrogen bonding, the binding distance is 2.54 nm. the results of infrared spectroscopy and circular dichroism method showed that two Dextromethorphan Hydrobromide added two level structure of the influence of DNA. UV absorption spectroscopy, ionic strength experiments, viscosity, melting temperature and experiment with single stranded DNA (ssDNA) results show that the combined effect of Dextromethorphan Hydrobromide and DNA is intercalation. The docking results showed that the two combination in the mode of intercalation, in the process of combining hydrogen bonds play an important role. Cyclic voltammetry and differential pulse voltammetry. The results showed that DNA was added to make the peak potential of Dextromethorphan Hydrobromide shifted. Using acridine orange (AO) as a probe of neomycin sulfate and by interaction of Barone sulfate peptide and DNA. Fluorescence quenching and time-resolved fluorescence spectroscopy results showed that neomycin sulfate / sulfuric acid azithromycin and Barone AO-DNA is a static quenching process. In 291 K, neomycin sulfate and sulfuric acid by Barone and AO-DNA binding constants were 6.70 * 103 and 1.44 * 103 L - mol-1. Delta H, Delta S and Delta G showed that neomycin sulfate / Barone sulfate kanamycin and AO-DNA by van Edward force and hydrogen bonding. Infrared spectroscopy and circular two color spectrometry results show that neomycin sulfate sulfate / Barone Two adding the lignin structure of DNA was influenced. The ionic strength experiments, viscosity, melting temperature and ssDNA effect experiment and experimental results show that neomycin sulfate / Barone sulfate kanamycin and DNA in groove pattern combining. Molecular docking method further showed that neomycin sulfate sulfur acid / Barone zymoid combination in DNA groove A-T rich area. By using spectroscopy, viscosity and molecular docking method was studied by using ethidium bromide (EB) as a fluorescence probe interaction of micronomicin / tobramycin and DNA. Fluorescence quenching and time-resolved fluorescence spectroscopy results show that micronomicin / tobramycin and the role of EB-DNA is static quenching at different temperatures are obtained. The process of micronomicin / tobramycin and EB-DNA binding constants and binding sites, Delta H, Delta S and delta G results indicated that micronomicin / EB-DNA and tobramycin by van Edward force and hydrogen bond. . infrared spectroscopy and circular dichroism method showed that two micronomicin / tobramycin adding two structure of DNA was influenced. The ionic strength experiments, viscosity, melting temperature and experiment of single stranded DNA experimental results showed that the micronomicin / role model and DNA for groove tobramycin with the show. The molecular docking method of micronomicin / tobramycin and DNA in groove combination mode, play an important role in the process of combining hydrogen bonds.

【學位授予單位】：長春師范大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R96;O657.3

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