本文選題：咪唑類衍生物 + 全氟化合物　； 參考：《河南師范大學(xué)》2017年碩士論文

【摘要】：一直以來,抗炎抗菌藥物藥理性和污染物的毒理性研究受到國(guó)內(nèi)外科學(xué)研究者的廣泛關(guān)注,這些物質(zhì)可以通過飲食、呼吸以及皮膚接觸等方式進(jìn)入體內(nèi),與蛋白質(zhì)等生物大分子進(jìn)行直接或者間接的作用,從而影響蛋白質(zhì)的功能及性質(zhì),對(duì)人體帶來危害,所以其活性成分與蛋白質(zhì)的作用機(jī)制相關(guān)課題是現(xiàn)代醫(yī)學(xué)、化學(xué)及生物學(xué)的研究熱點(diǎn)。蛋白質(zhì)是承載著生命活動(dòng)各項(xiàng)功能,對(duì)生命活動(dòng)有主導(dǎo)性的作用,它能夠和多種外源性藥物及污染物進(jìn)行可逆性結(jié)合,因而研究此類小分子對(duì)蛋白質(zhì)構(gòu)象變化的影響是化學(xué)領(lǐng)域中備受關(guān)注的重要課題之一。近年來,熒光分析法因其在化學(xué)檢測(cè)、生物樣品分析等方面的重要應(yīng)用價(jià)值而引起越來越多化學(xué)研究工作者的關(guān)注。目前,研究人員已經(jīng)做了諸多關(guān)于小分子對(duì)蛋白質(zhì)構(gòu)象變化影響的研究,但是更為深入的解釋其作用機(jī)制方面尚不完善。因此,對(duì)小分子與蛋白質(zhì)的結(jié)合機(jī)制和作用機(jī)理的深入研究仍是一項(xiàng)有意義的工作。針對(duì)上述調(diào)研,本論文主要介紹的內(nèi)容包括:1、設(shè)計(jì)并合成有代表性的三種咪唑類衍生物1-(4-溴苯基)-2,4,5-三苯基-1H-咪唑(BPTI),1-(4-溴苯基)-2-(4-氟苯基)-4,5-二苯基-1H-咪唑(BFDI)和1-(4-溴苯基)-4,5-二苯基-2-(噻吩-2-基)吡啶-2-基)-1H-咪唑(BDTI)。通過光譜法和分子對(duì)接研究三種咪唑衍生物與人血清白蛋白的作用機(jī)制,考察相互作用的結(jié)構(gòu)特征;通過熱力學(xué)數(shù)據(jù)計(jì)算焓變和熵變等數(shù)值進(jìn)而分析作用力類型;利用非輻射能量轉(zhuǎn)移方法計(jì)算結(jié)合距離,最后通過紅外光譜和圓二色譜等證實(shí)BPTI/BFDI/BDTI對(duì)人血清蛋白構(gòu)象的影響。2、利用熒光光譜法、紫外可見吸收光譜法、紅外光譜法以及分子模擬研究了抗菌劑的主要成分三氯生(TCS)和三氯卡班(TCC)與胃蛋白酶的相互作用,擬合計(jì)算不同溫度下TCS/TCC與胃蛋白酶相互作用的結(jié)合常數(shù)及位點(diǎn)數(shù),定量分析其對(duì)胃蛋白酶二級(jí)結(jié)構(gòu)的影響,并通過熱力學(xué)參數(shù)確定TCS/TCC與胃蛋白酶之間的作用力類型,最后利用分子模擬法確定TCS/TCC與胃蛋白酶的結(jié)合位置。3、通過光譜法和分子對(duì)接方法研究全氟辛酸(PFOA)和全氟壬酸(PFNA)與胃蛋白酶的結(jié)合模式,比較它們與胃蛋白酶的結(jié)合能力差異;同時(shí),利用時(shí)間分辨熒光等方法對(duì)PFOA和PFNA與胃蛋白酶猝滅機(jī)制加以印證,并通過熱力學(xué)參數(shù)分析其相互作用過程中的主要作用力類型。除此之外,還通過UV-vis、FT-IR、三維熒光解釋二者對(duì)胃蛋白酶的構(gòu)象影響,最后通過圓二色譜以及分子對(duì)接進(jìn)一步證實(shí)實(shí)驗(yàn)結(jié)果。
[Abstract]:For a long time, the study of anti-inflammatory and antimicrobial agents and toxicology of pollutants has received extensive attention from scientific researchers at home and abroad. These substances can enter the body through diet, breathing and skin contact. Biological macromolecules such as proteins act directly or indirectly, thus affecting the functions and properties of proteins and harming the human body. Therefore, modern medicine is the subject related to its active components and the mechanism of action of proteins. Research focus in chemistry and biology. Protein is the carrier of various functions of life activities, has the leading role in life activities, it can be combined with a variety of exogenous drugs and pollutants for reversible binding, Therefore, the study of the effect of these small molecules on the conformation change of proteins is one of the most important topics in the field of chemistry. In recent years, fluorescence analysis has attracted more and more attention of chemical researchers because of its important application value in chemical detection and biological sample analysis. At present, researchers have done a lot of research on the effect of small molecules on protein conformation, but it is not perfect to explain the mechanism of protein conformation. Therefore, it is still a meaningful work to study the binding mechanism and action mechanism of small molecules and proteins. In response to the above research, The main contents of this thesis include the design and synthesis of three typical derivatives of imidazole (1: 1, 1-4-bromophenyl) and 1-4-bromophenyl-4-4-bromophenyl-4-diphenyl-4-diphenyl-1H-imidazolium BFDI) and 1-4-bromophenyl-4-4-diphenyl-5-diphenyl-2-(phenothiophenyl)-5-diphenyl-2-(Phenothiophenyl)-5-diphenyl-2-(phenothiophenyl) Pyridine-2-pyridyl-1H-imidazolium (BDTI). The interaction mechanism of three imidazole derivatives with human serum albumin was studied by means of spectroscopic method and molecular docking, and the structural characteristics of the interaction were investigated, the enthalpy change and entropy change were calculated by thermodynamic data, and the types of force were analyzed. The binding distance was calculated by non-radiative energy transfer method. Finally, the influence of BPTI/BFDI/BDTI on the conformation of human serum protein was confirmed by infrared spectroscopy and circular dichroism. The interaction between TCS/TCC and pepsin was studied by infrared spectroscopy and molecular simulation. The binding constants and sites of the interaction between TCS/TCC and pepsin at different temperatures were calculated. The effect of pepsin on the secondary structure of pepsin was quantitatively analyzed, and the type of interaction between TCS/TCC and pepsin was determined by thermodynamic parameters. Finally, the binding sites of TCS/TCC and pepsin were determined by molecular simulation method. The binding modes of PFOAA and PFNA with pepsin were studied by means of spectral method and molecular docking method, and their binding ability with pepsin was compared. At the same time, the quenching mechanism of PFOA and PFNA with pepsin was verified by time-resolved fluorescence method, and the main interaction force types in the process of interaction were analyzed by thermodynamic parameters. In addition, the conformation of pepsin was explained by UV-vis-FT-IR and three-dimensional fluorescence. The experimental results were further confirmed by circular dichroism and molecular docking.
【學(xué)位授予單位】：河南師范大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R96;O657.3

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