分子光谱法研究血红蛋白和小分子的相互作用

发布时间：2018-07-03 17:42

本文选题：血红蛋白 + 小分子　；参考：《郑州大学》2014年硕士论文

【摘要】：蛋白质大分子是生物体内除水外含量最大的成分，它与生命以及生命活动密切相关。各种生物小分子，无论是药物还是毒物，进入机体后，都会与之发生反应，影响着机体的新陈代谢。蛋白质与小分子结构类似物的相互作用研究可以有助了解各类小分子物质在体内的代谢及药理毒理研究，同时也为小分子药物的设计和筛选中考虑不同的官能团效应提供有效信息。本文以血红蛋白（Hb）大分子，联苯双酯（DDB）及其结构类似物、五种生物碱、2'-脱氧基-2'-β-氟代-4'-叠氮基胞嘧啶核苷（FNC）、四种三苯甲烷类染料及中性红小分子为研究对象，使用荧光光谱法，紫外可见吸收光谱法以及分子模拟技术研究了大分子与小分子的相互作用。结果表明这五类物质均能引起Hb荧光猝灭，猝灭机理均为静态猝灭。各类结构类似物与Hb的结合常数因其官能团的不同而有差异，DDB及其结构类似物中DDB的结合常数最大，类似物(III)的结合常数最小；五种生物碱中氨茶碱的结合常数最大，二羟丙茶碱的结合常数最小；FNC与人血红蛋白（HHb）和牛血红蛋白（BHb）的结合常数为BHb＞HHb;四种三苯甲烷类染料中溴邻苯三酚红的结合常数最大，溴甲酚绿的结合常数最小。相互作用力DDB及其类似物与HHb，五种生物碱与HHb，FNC与BHb,三苯甲烷染料与BHb，中性红与BHb均为疏水作用力和静电引力，FNC和HHb主要通过范德华力和氢键。五类物质与Hb之间的结合距离小于8nm，发生了能量转移。紫外可见吸收光谱以及同步和三维荧光光谱法显示五类物质使得Hb的构象发生改变。分子模拟结果显示不同结构的类似物与Hb的结合位点也有差异，，这与实验结果相互印证。
[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.
【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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