基于酶功能化碳纳米管包覆硅胶柱色谱的黄酮类化合物抑制黄嘌呤氧化酶活性的构效关系研究

项目名称： 基于酶功能化碳纳米管包覆硅胶柱色谱的黄酮类化合物抑制黄嘌呤氧化酶活性的构效关系研究

项目编号： No.21205126

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 分析化学

项目作者： 孙小明

作者单位： 中国科学院兰州化学物理研究所

项目金额： 25万元

中文摘要： 酶抑制剂的开发是新药创制的一个重要途径，而定量构效关系研究则是以酶为靶点的药物设计和开发的主要手段。本项目从功能材料开发和模式创新着手，致力于酶功能化碳纳米管包覆硅胶柱色谱特异分离技术的创新研究。通过制备一种以酶为活性靶点、碳纳米管为吸附中心、硅胶为分离介质的酶功能化碳纳米管包覆硅胶，拟构建一种特异性亲和吸附、液相色谱高效分离和活性评价相结合的分离模式。以天然产物中的黄酮类化合物为研究对象，考察其在基于黄嘌呤氧化酶的功能化色谱填料上的色谱行为，建立在线活性评价方法，并结合偏最小二乘判别（PLS-DA）的化学计量学方法，对其抑制黄嘌呤氧化酶活性的构效关系进行模式识别分析，从而找到影响黄酮类物质抑制黄嘌呤氧化酶活性的关键因素。通过本项目的实施，为天然产物的构效关系研究提供了一种新思路，也可能通过该方法筛选与疾病相关的药物及先导化合物，为疾病防治奠定基础。

中文关键词： 黄嘌呤氧化酶；黄酮类化合物；碳纳米管；高效液相色谱；构效关系

英文摘要： The development of enzyme inhibitors is an important pathway for new drug discovery. Meanwhile, QSAR studies are the major means by which the enzyme-targeted drug are designed and developed. In this project, an innovation research, including the development of functionalized material and innovation model, will be performed. An silica gel column coated with enzyme functionalized carbon nanotubes (ECNTs-SC), including enzyme target, adsorption center and separation medium will be prepared to provide a new separation model. This model would gather the advantage of specific affinity adsorption, high performance separation of liquid chromatography and bioassay evaluation. In this project, the chromatographic behaviors of flavonoids on the ECNTs-SC will be investigated and the on-line evaluation method of xanthine oxidase inhibitory activity will be set up. Pattern recognition between the flavonoids structure and the xanthine oxidase inhibitory activity will be calculated by a chemometric method of partial least squares discrimination analysis (PLS-DA). Consequently, the key factors of xanthine oxidase inhibitory activity of flavonoids will be elucidated. The implementation of the project will undoubtedly provide a new idea for the QSAR studies. Furthermore, some drugs or lead compounds may be discovered by this metho

英文关键词： xanthine oxidase；flavonoids；carbon nanotubes；HPLC；QSAR