本文選題：血紅蛋白 + 小分子��； 參考：《鄭州大學(xué)》2014年碩士論文

【摘要】：蛋白質(zhì)大分子是生物體內(nèi)除水外含量最大的成分，它與生命以及生命活動(dòng)密切相關(guān)。各種生物小分子，無論是藥物還是毒物，進(jìn)入機(jī)體后，都會(huì)與之發(fā)生反應(yīng)，影響著機(jī)體的新陳代謝。蛋白質(zhì)與小分子結(jié)構(gòu)類似物的相互作用研究可以有助了解各類小分子物質(zhì)在體內(nèi)的代謝及藥理毒理研究，同時(shí)也為小分子藥物的設(shè)計(jì)和篩選中考慮不同的官能團(tuán)效應(yīng)提供有效信息。 本文以血紅蛋白（Hb）大分子，聯(lián)苯雙酯（DDB）及其結(jié)構(gòu)類似物、五種生物堿、2'-脫氧基-2'-β-氟代-4'-疊氮基胞嘧啶核苷（FNC）、四種三苯甲烷類染料及中性紅小分子為研究對(duì)象，使用熒光光譜法，紫外可見吸收光譜法以及分子模擬技術(shù)研究了大分子與小分子的相互作用。結(jié)果表明這五類物質(zhì)均能引起Hb熒光猝滅，猝滅機(jī)理均為靜態(tài)猝滅。各類結(jié)構(gòu)類似物與Hb的結(jié)合常數(shù)因其官能團(tuán)的不同而有差異，DDB及其結(jié)構(gòu)類似物中DDB的結(jié)合常數(shù)最大，類似物(III)的結(jié)合常數(shù)最�。晃宸N生物堿中氨茶堿的結(jié)合常數(shù)最大，二羥丙茶堿的結(jié)合常數(shù)最小；FNC與人血紅蛋白（HHb）和牛血紅蛋白（BHb）的結(jié)合常數(shù)為BHb＞HHb;四種三苯甲烷類染料中溴鄰苯三酚紅的結(jié)合常數(shù)最大，溴甲酚綠的結(jié)合常數(shù)最小。相互作用力DDB及其類似物與HHb，五種生物堿與HHb，F(xiàn)NC與BHb,三苯甲烷染料與BHb，中性紅與BHb均為疏水作用力和靜電引力，F(xiàn)NC和HHb主要通過范德華力和氫鍵。五類物質(zhì)與Hb之間的結(jié)合距離小于8nm，發(fā)生了能量轉(zhuǎn)移。紫外可見吸收光譜以及同步和三維熒光光譜法顯示五類物質(zhì)使得Hb的構(gòu)象發(fā)生改變。分子模擬結(jié)果顯示不同結(jié)構(gòu)的類似物與Hb的結(jié)合位點(diǎn)也有差異，，這與實(shí)驗(yàn)結(jié)果相互印證。
[Abstract]:Protein macromolecules are the most abundant components except water, which are closely related to life and life activities. A variety of biological small molecules, whether drugs or poisons, will react with the organism when it enters the body, affecting the metabolism of the body. Studies on the interactions of proteins with structural analogues of small molecules can help to understand the metabolism and pharmacological toxicology of various small molecules in vivo. It also provides useful information for the design and screening of small molecular drugs. In this paper, hemoglobin (HB) macromolecules, diphenyl diesters (DDB) and their structural analogues, five alkaloids, two alkaloids, deoxy-2- 尾 -fluoro-4-azido-cytosine nucleoside (FNC), four triphenylmethane dyes and neutral red small molecules were studied. The interaction between macromolecules and small molecules was studied by UV-vis absorption spectroscopy and molecular simulation. The results show that these five kinds of substances can cause the fluorescence quenching of HB, and the quenching mechanism is static quenching. The binding constants of various structural analogues to HB are different because of their functional groups. In DDB and its structural analogues, the binding constants of DDB and analogues (III) are the largest, and the binding constants of aminophylline are the largest among the five alkaloids. The binding constants of dihydroxypropylline with human hemoglobin (HHB) and bovine hemoglobin (BHB) were minimum, and the binding constants of bromo-pyrogallol red and bromocresol green were the largest among the four triphenylmethane dyes. The interaction forces DDB and its analogues with HHb, five alkaloids with HHbFNC and BHb, triphenylmethane dyes with BHb, neutral red with BHb are hydrophobic forces and electrostatic gravitational forces, FNC and HB are mainly via van der Waals force and hydrogen bond. The binding distance between the five kinds of substances and HB is less than 8 nm, which results in energy transfer. UV-visible absorption spectra and synchronous and three-dimensional fluorescence spectra showed that the conformation of HB was changed by five kinds of substances. The molecular simulation results show that the binding sites of the analogues with different structures are also different, which is consistent with the experimental results.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R96

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