G-四聚体是目前广受关注的具有特殊结构的单链寡聚核苷酸，其在染色体的端粒区域以及原癌基因的启动子区域高度表达，是抗癌药物的潜在靶标。同时它也被灵活地运用到各种传感模型中作为信号识别探针。对于G-四聚体的小分子配体的筛选主要借助光学手段，而具有简单、快速、低成本以及仪器微型化等强劲优势的电化学方法筛选配体的策略还没有得到足够的重视。同时目前筛选到的G-四聚体小分子配体通常具有光学特性，而具有电化学活性的小分子配体还鲜有报道，成为G-四聚体研究的空白领域。本课题拟建立系统的研究G-四聚体与电活性小分子相互作用的方法，筛选获得高特异性的G-四聚体电活性小分子配体，在此基础上以G-四聚体/电活性配体复合物作为一种新的信号报告元件发展无标记均相电化学传感新模型；同时通过电化学的手段筛选能够有效抑制端粒酶活性的配体和特异性结合原癌基因启动子区域序列的配体，为抗癌药物的开发和筛选提供新的思路。

The research on G-quadruplex has recently attracted much attention due to its special structure. G-quadruplex DNA becomes a potential target of anticancer drugs because it highly presents in telomeres and the promoter regions of proto-oncogenes. At the same time, G-quadruplex acting as signal read-out element can be flexibly designed into various detection strategies. Up to now, the screening of G-quadruplex binding ligands is mainly based on spectroscopic methods. And most of assays based on G-quadruplex/ligand complexes which often possess optical characteristics focus on spectrometry such as colorimetry or fluorimetry with the essential use of bulky and expensive optical instruments. The electroactive ligand of G-quadruplex which is suitable for portable and cost-effective electrochemical assays as electrochemical indicator has not been widely reported yet. In this proposal, we will systematically investigate the interaction between G-quadruplexes and electroactive molecules, and construct screening method for the electrochemical ligands of G-quadruplexes with high affinity and specificity. A novel signal read-out mode based on the strong affinity between G-quadruplex and electroactive ligand will be used to develop homogeneous label-free electrochemical biosensing systems. The screening of inhibitors towards telomerase and specific ligands of the promoter regions of proto-oncogenes based on electrochemical methods will provide new direction for the development of anti-cancer drugs.