几种头孢菌素类抗生素与生物大分子的亲和作用

发布时间：2018-06-02 10:21

本文选题：头孢菌素 + 重金属离子　；参考：《湖北师范大学》2017年硕士论文

【摘要】：抗生素对多数常见菌抑制效果良好。在日常生活中,抗生素常被用来治疗因细菌感染而引发的多种疾病;有些畜牧养殖厂为预防牲畜细菌感染而大面积使用抗生素;有些不法商家甚至使用抗生素促使牲畜快速生长,危害巨大。人体、牲畜使用的抗生素在体内吸收往往不完全,会随代谢产物排出体外,与大量过期的抗生素一起流入环境体系,破坏生态环境。头孢菌素类抗生素种类繁多,对大多数细菌(如革兰氏阴或阳性菌)所引发的细菌感染均有良好的抑菌作用。头孢菌素最常用的分类方法为依据抗菌特点而分类,分为四代,其种类居各类抗生素首位,且不同头孢菌素分子结构之间存在较大差异。工业生产产生的重金属离子,经水体、土壤、大气的传递与运输,广泛分布在环境中。具有强遗传毒性的重金属离子危害极大,一旦进入食物链,即使经过多层食物链的传递也无法从生物体内代谢除去,从而不间断地在重要器官内吸附、积累,严重威胁人类和动物健康。本文旨在利用生物化学方法,对比研究分子结构上差异性较大的头孢菌素与生物大分子的亲和作用,考察头孢菌素分子母核侧链连接不同基团对头孢菌素-生物大分子亲和作用所造成的影响,进而分析头孢菌素分子结构-亲和性对应关系。引入强遗传毒性重金属离子,考察重金属离子与头孢菌素之间的协同效应。本论文共分为五章,分别为:第一章:主要介绍了现今环境中普遍存在的抗生素以及重金属离子,分别阐述抗生素与重金属离子的使用、排放以及污染现状;归纳现今用作分析药物小分子-生物大分子相互作用的主要研究方法,概括研究现状;从总体研究思路,文章立题意义,以及本文研究特点等方面概述。第二章:以头孢克洛(第二代头孢菌素)、头孢克肟(第三代头孢菌素)为研究对象,采用紫外吸收光谱、荧光光谱、分子模拟技术、电化学方法考察这两种头孢菌素与生物大分子DNA相互作用时的作用机理、结合模式。研究抗生素分子结构-作用机理之间的关联。同时考察温度、离子强度、变性剂、热变性、作用时间、重金属离子等因素对头孢菌素与DNA相互作用的影响。第三章:借助紫外吸收光谱、荧光光谱、分子模拟等方法研究头孢氨苄(第一代头孢菌素)、头孢克肟(第三代头孢菌素)与牛血清白蛋白的相互作用。比较并分析实验中所引入的两种头孢菌素分子结构上存在的差异;比较相互作用机理;判断主要作用力;确定结合位点;分析所加药物对氨基酸残基所处微环境的影响;实验中选用计算机辅助设计,从分子结构角度深入考察作用体系具体键联信息;同时,选择性添加重金属离子,分析其对头孢克洛(或头孢克肟)与牛血清白蛋白亲和作用的影响。第四章:选取四种头孢菌素(头孢氨苄、头孢克洛、头孢克肟以及头孢吡肟),选用光分析方法、电分析方法、以及分子模拟方法分析四种头孢菌素与人血清白蛋白的相互作用。对比实验中所引入的四种头孢菌素分子结构上所存在的差异;判断作用机理;确定主要作用力;确定结合位点;选用交流阻抗法考察反应体系电子的转移情况,并深入探究电子发生转移原因;实验中选用圆二色光谱、三维荧光光谱、同步荧光光谱法分析这四种头孢菌素的加入对蛋白质分子空间构象的影响;考察具有强遗传毒性的重金属离子与头孢菌素之间的协同效应;同时结合分子模拟技术,深入考察四种头孢菌素与人血清白蛋白结合的具体键联信息。第五章:总结全文并得出实验结论,展望后续工作,为头孢菌素结构-亲和性研究提出思考和建议。
[Abstract]:Antibiotics have a good effect on most common bacteria. In daily life, antibiotics are often used to treat a variety of diseases caused by bacterial infection; some livestock farms use antibiotics for the prevention of bacterial infection in livestock. Some illegal businesses even use antibiotics to promote rapid growth of livestock. The antibiotics used in the body are often not completely absorbed in the body. They will be discharged in vitro with the metabolites and flow into the environment system with a large number of overexpired antibiotics and destroy the ecological environment. There are a wide variety of cephalosporins, which have good bacteriostasis for the bacterial infection caused by most bacteria (such as gram-negative or positive bacteria). The most commonly used classification method is classified into four generations according to the characteristics of antibacterial activity, and its species ranks first in various kinds of antibiotics, and there are great differences between different molecular structures of cephalosporins. Heavy metal ions produced by industrial production are widely distributed in the environment through the transmission and transportation of water, soil and atmosphere. Heavy metals with strong genetic toxicity are found in the environment. Once entering the food chain, even through the food chain, even through the transmission of the multi-layer food chain, it can not be removed from the organism, thus uninterruptedly adsorbing, accumulating and threatening human and animal health in an important organ. This paper aims to use biochemical methods to compare and study cephalosporins with large differences in molecular structure. The influence of different groups of cephalosporins on the affinity of cephalosporins and biological macromolecules by the side chain of cephalosporins was investigated, and the corresponding relationship between the molecular structure and affinity of cephalosporins was analyzed. The strong genotoxic heavy metal ions were introduced to investigate the synergistic effect between heavy metal ions and cephalosporins. This paper is divided into five chapters: Chapter 1: the first chapter is the introduction of the prevailing antibiotics and heavy metal ions in the present environment. The use, emission and pollution status of antibiotics and heavy metal ions are described respectively, and the main research methods used to analyze the interaction of small molecules and macromolecules are summarized and summarized. The second chapter: using cefaclor (second generation cephalosporins) and cefixime (third generation cephalosporins) as the research object, using UV absorption spectra, fluorescence spectra, molecular simulation technology and electrochemical methods to investigate the two cephalosporins and biological fractions. The interaction mechanism of the sub DNA interaction, combined with the mode. The relationship between the molecular structure of antibiotics and the mechanism of action. The influence of temperature, ionic strength, denaturant, thermal denaturation, action time, heavy metal ions on the interaction of cephalosporin and DNA. The third chapter: UV absorption, fluorescence, molecular simulation To study the interaction between cefamoxin (first generation cephalosporin) and cefixime (third generation cephalosporins) and bovine serum albumin. Compare and analyze the differences in the molecular structure of the two kinds of cephalosporins introduced in the experiment; compare the interaction mechanism; determine the main force; determine the binding site; analyze the added drugs to ammonia. The effect of the microenvironment on the base acid residues; in the experiment, the computer aided design was selected to examine the specific bond information from the molecular structure angle. At the same time, the effect of the selective addition of heavy metal ions on the affinity and effect of cefaclor (or cefixime) with bovine serum albumin was analyzed. The fourth chapter: the selection of four cephalosporins (head) The interaction between four cephalosporins and human serum albumin was analyzed by PHOTOANALYSIS, electroanalysis and molecular simulation. The differences in the molecular structure of the four cephalosporins introduced in the experiment were compared, the mechanism of action was judged and the main force was determined. To determine the binding site, use the AC impedance method to investigate the electron transfer in the reaction system, and to explore the cause of the electron transfer. In the experiment, the effect of the four cephalosporins on the spatial conformation of the protein molecules was analyzed by using the circular two color spectrum, the three-dimensional fluorescence spectrum and the synchronous fluorescence spectrum, and the strong genotoxicity was investigated. The synergistic effect between heavy metal ions and cephalosporins; at the same time combined with molecular simulation technology, the specific bond information of the binding of four cephalosporins to human serum albumin was examined in depth. The fifth chapter: summarize the full text and draw the conclusion of the experiment, and look forward to the follow-up work, and put forward some thoughts and suggestions for the study of cephalosporin's structure and affinity.
【学位授予单位】：湖北师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R96

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