项目名称: 乙酰胆碱酯酶功能结构域化学模拟及有机磷农药仿生识别分析研究
项目编号: No.31501571
项目类型: 青年科学基金项目
立项/批准年度: 2016
项目学科: 农业科学
项目作者: 王淼
作者单位: 中国农业科学院原子能利用研究所
项目金额: 20万元
中文摘要: 乙酰胆碱酯酶(AChE)抑制法是有机磷农药残留快速检测和毒理分析的主流方法。但由于AChE酶源和种类多样,且对环境条件要求严格,不同操作间的可比性不佳,严重影响了方法的稳定性和可靠性,造成误判可能。 本研究拟采用腙类和肟类分子模拟AChE催化位点,采用寡肽、带电胶束和分子印迹聚合物模拟识别与结合位点,并偶联成为复合材料,人工合成化学仿生酶模拟AChE的核心功能结构域,使其具有对底物乙酰胆碱的结合、水解催化及被有机磷农药抑制的活性,以实现对有机磷农药的有效识别和检测。同时基于结合、催化及抑制数据的统计分析和构效关系研究,实现对有机磷农药毒性的判断。本研究期望在理论模型和生物模型之间,构建一个化学仿生模型,简化条件参数,进行数据挖掘分析,并与有机磷农药的毒理学数据进行对应解析和相互验证,建立起有机磷农药快速定性、定量分析新方法,并为毒性机制分析及动物实验替代技术提供新的思路。
中文关键词: 分子识别;有机磷农药;化学模拟;仿生分析信号机制;乙酰胆碱酯酶
英文摘要: The inhibition effect of organophosphate pesticide to Acetylcholinesterase (AChE) can be used for pesticides residues rapid testing and toxicology assays. However,because of the diversity of enzyme resources and species,AChE was greatly influenced by environmental conditions. Thus the stability and reliability of enzyme inhibition assay were seriously affected. This study intends to synthetic functional bionic materials to simulate the functional domains of AChE,and to mimicits core functions, by the ways of mimic catalytic site with hydrazones and oximes and mimic specific binding sites with oligopeptides, charged micelles and molecularly imprinted polymers. Combining the two parts together, artificial enzyme complex were obtained to realize the specific combination and quantitative detection of organophosphate pesticide. At the same time, based on the data of the material combination and catalytic inhibition and structure-activity relationship studies, toxicity of organophosphorus pesticides could be qualitative judged..This study would build a new chemical bionic model as a bridge, between theoretical calculation model and real biological experiment. And under the simplified condition with less environmental parameters, researches, data collection and calculation could be carried on easily. And with the corresponding resolution and analysis of organophosphorus pesticide toxicology data, a new thought could be provided, which is be conducive to the organophosphate pesticide rapid detection, toxicology assay, toxic mechanism analysis and animal experiment in vitro alternative technologies.
英文关键词: Molecular Recognition;Organophosphorate Pesticides ;Chemical Mimic ;Bionic analysis signal mechanism; Acetylcholinesterase