金属基单双链DNA识别探针的设计合成及其在基因传感检测中的应用

项目名称： 金属基单双链DNA识别探针的设计合成及其在基因传感检测中的应用

项目编号： No.20805041

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 金属学与金属工艺

项目作者： 汪庆祥

作者单位： 闽南师范大学

项目金额： 18万元

中文摘要： 作为电化学基因传感器的关键组件之一，新型杂交指示剂的设计和开发一直是生命分析领域的研究热点。然而目前广泛使用的指示剂在检测条件下都呈正电荷属性，它们与单、双DNA之间的非特异性静电作用在很大程度上制约了传感器基因检测的准确性。 本课题拟以含羟基、羧基、巯基等负电荷配位基团的分子（如氨基酸、吡啶羧酸等）作为电荷控制配体，并以二吡啶[3,2-a:2',3'-c]吩嗪等芳环平面分子为嵌插配体合成电中性金属配合物以降低配合物与DNA之间的非特异性结合作用。通过电化学方法获得该类配合物与双、单链DNA之间的动力学和热力学作用参数，讨论电荷控制配体的立体构型、大小、电荷数、芳香性等特征对配合物的DNA结构识别功能的影响。筛选出识别性能优越的配合物作为杂交指示剂应用于DNA电化学传感器中，建立特定基因序列电化学检测的完整方法。

中文关键词： 电中性金属配合物；单双链DNA；电化学传感器；杂交指示剂

英文摘要： As the most important part of the gene electrochemical biosensor, the designing and development of new hybridization indicators is always the hot topic in bio-analytical areas. However, due to the positive charge property of the widely used indicators, they often showed nonspecific electrostatic interaction with single-stranded (ss-) and double-stranded (ds-) DNA, which greatly limited the analytical performance of the DNA biosensors. In this project, the electrically neutral metal complexes that using the carboxyl, hydroxyl and sulfydryl groups-contained negatively charged molecules (like amino acid, picolinic acid, et al.) as the charged ligands and the aromatic ring planner molecules, like bipyridine [3,2-a:2',3'-c] phenazine as the intercalative ligands were proposed to be used as the DNA hybridization indicator. Because the positive charges of the complexes were eliminated, the non-specific electrostatic interaction the synthesized complexes with DNA could be completely precluded. In addition, the dynamic and thermodynamic binding parameters of the complexes with ssDNA and dsDNA are planned to obtained through electrochemical methods, and also the influences of spatial configuration, size, charge number, aromaticity of the charge-controlling ligands on the DNA recognition ability are proposed to be analyzed. Ultimately, we plan to use the highly selective electrically neutral metal complexes as electrochemical hybridization indicator in DNA biosensor and establish an integrated electrochemical method for the analysis of specific gene fragments.

英文关键词： Electrically neutral metal complexes; Single-stranded (ss-) and double-stranded (ds-) DNA; Electrochemical biosnesor; Hybridization indicator