DNA特殊结构荧光探针的设计、合成和生物活性研究

项目名称： DNA特殊结构荧光探针的设计、合成和生物活性研究

项目编号： No.21272181

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 翁小成

作者单位： 武汉大学

项目金额： 80万元

中文摘要： DNA特殊结构的识别对于研究生命活动基本规律和疾病发生机制，建立疾病诊断新方法有重要的意义。本项目拟以DNA特殊结构为靶目标，进行荧光探针分子的设计、合成和生物活性研究。主要研究内容包括（1）以错配（mismatch）、突起（bulge）、发卡结构（hairpin）和G-四链体为靶标的探针分子设计与合成；（2）探针分子与DNA特殊结构相互作用的检测，通过荧光检测评价探针分子的可行性，并拟通过各光谱学方法、核磁共振研究、计算机模拟等手段建立探针与靶标的结合模型，指导分子探针的进一步优化和筛选；（3）进行探针分子对于真实基因突变序列的检测研究，检测探针分子在错配修复机制缺失的细胞中的荧光响应，拓展探针分子的应用前景。此项目的实施，对于研究DNA的结构多态性和动态性的变化规律，建立与DNA突变相关重大疾病的早期诊断方法，推动分子荧光显像技术在生命科学、医学方面的应用有着重要的学术价值和应用前景。

中文关键词： DNA；特殊结构；荧光探针；有机合成；生物活性

英文摘要： The recognition of the special structure of DNA is very important and with great significance for the studding of the basic principle of life and disease mechanisms. It is also very important to the establishment of the new methods of disease diagnosis. The project intends to research the design and synethsize of fluorescent probe molecule, and their biological activities to the special structure of DNA. The research topics include: (1) The design and synthesis of the fluorescent probes target mismatch, bulge, hairpin structure and G-quadruplex; (2) The interaction detection of probe molecule and the special structure of DNA. Firstly, we will study the bioligcal activity of the probe with fluorescence detection. Then establish the proposed model of the interaction between probes and targets by various spectroscopic methods, such as NMR studies, computer simulation and other means, which is useful to guide the further optimize and screening of molecular probes; (3) The detection of true gene mutation sequence by the probe molecules. We will study the fluorescence response of the probe molecules in the cells which have the mismatch repair mechanism deficiency. These researchs can expand the prospects for the application of probe molecules. This project is useful to study the structure of DNA polymorphism and dynam

英文关键词： DNA；special structure；fluorescent probe；organic synthesis；biological research