项目名称： 新型荧光DNA修饰碱基的分子设计及其分子识别能力的理论研究

项目编号： No.21503119

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 数理科学和化学

项目作者： 张来斌

作者单位： 曲阜师范大学

项目金额： 21万元

中文摘要： 荧光核酸碱基类似物在DNA自动测序、探测DNA杂化、抗体免疫分析、疾病诊断和抗癌药物分析等方面具有重要而广泛地应用，因此设计和开发具有良好荧光活性的碱基类似物是核酸研究领域的热点课题之一。本项目围绕核酸修饰的相关问题，拟对天然碱基进行改良修饰，设计若干新型碱基类似物，并利用理论化学方法探讨其结构性质、电子性质、稳定性、电子光谱性质以及新型DNA链的相关性质；阐明其电子光谱对生物微环境（包括配对模式、堆积模式、溶剂效应、金属离子和纳米金团簇等）的响应识别能力，建立相应的分子识别标度，从而考查新设计碱基在研究碱基错配、基团作用和分子识别方面的可能性；总结修饰碱基与天然碱基在光谱性质上的差异和不同修饰策略所带来的影响，获得其结构与性质参数之间的内在相关性，为荧光核酸碱基类似物的实验设计、合成及应用提供一些科学依据和理论参考。

中文关键词： 核酸碱基类似物；分子设计；分子识别；分子模拟；荧光性质

英文摘要： The design and development of fluorescent base analogues is one of the research hotspots in nucleic acid, primarily motivated by the fact that these analogues have important and widespread applications in DNA sequencing, DNA hybridization detection, antibody immune analysis, disease diagnosis, as well as anti-cancer drug analysis. The present work focuses on the structure modification of natural DNA bases with the aim of designing several base analogues that have improved and novel properties. The structures, electronic properties, stabilities, and electronic spectroscopy properties of them as well as the new DNA duplexes will be studied. The molecular recognition abilities of their electronic spectroscopy on local biological environments, including the base pairing, base stacking, solvents, metal ions, gold nanoclusters, etc., will be clarified, and the molecular recognition criterion will be build. Based on the results mentioned above, the potential applications of these newly designed base analogues in study of base mispair, group interactions, and molecular recognition would be explored. Finally, the effects of different modification strategies on the spectroscopies of DNA bases and the relationships between the structures and property would be summarized. The study conclusions were anticipated to be helpful on the design and synthesis of fluorescent base analogues experimentally.

英文关键词： nucleobase analogues;molecular design;molecular recognition;molecular simulations;fluorescent property