本项目研究具有生物活性的小分子对人类端粒G-四链体（G4）碱基损伤缺失产生的脱碱基位点的选择性识别及结构回稳机制。研究脱碱基位点的位置对G4稳定性及构象的影响，小分子各种环取代衍生物对G4不同位置脱碱基位点的识别及稳定化影响，以及环境条件如K+，Na+，分子拥挤等对G4结构及识别的影响。开展与结构完整的G4(不含脱碱基位点)及含脱碱基位点的ds-DNA的对比研究，采用电化学与各种谱学技术结合，筛选出对G4脱碱基位点具有高结合强度和选择性的小分子。分析识别作用力，阐明小分子对G4脱碱基位点特异性识别的关键结构要素，以及这种识别作用对G4稳定性的贡献，阐明识别原理。人类端粒G4与细胞繁殖是密切相关的。但由于G4序列中含有多个相邻的G碱基，与其它结构的DNA相比，易于氧化损伤产生脱碱基位点而使其结构失稳。因此阐明小分子的识别作用对深入理解小分子对G4活性的调制及基于G4的传感器研究有重要意义。

This project is aimed to study the selective recognition of human telomeric DNA G-quadruplex abasic site that is produced by nucleotide damage and base loss using small bioactive molecules as the probes and the mechanism of such binding-induced G-quadruplex restabilization. The effect of position of the abasic site on the G-quadruplex stabilization and conformation will be first investigated. On the basis of this knowledge, the recognition of G-quadruplexes with differently positioned abasic site will be explored using small molecules having various substituent groups. Additionally, various experimental conditions including K+, Na+, and molecular crowding will be tested for this specific recognition. In comparison with the intact G-quadruplexes not containing the abasic site and the duplexes instead containing the abasic site, the small molecules having high binding selectivity and specificity for the G-quadruplex abasic site will be screened using electrochemical and various spectrometric technologies. Analyzing the interaction forces, the decisively structural elements of the small molecules will be identified for the recognition. The contribution of the specific recognition on the G-quadruplex stability will be clarified and the recognition mechanism will be finally established. It is well known that human telomeric DNA G-quadruplexes are closely correlated to the cell proliferation. However, the G-quadruplexes contain numerous contiguous guanine bases and thus are more easily oxidized to generate the abasic site lesion in comparison with the other DNA structures, resuliting in destabilizing the G-quadruplexes. Thus, recognizing the abasic site using small molecules is of great importance for thoroughly understanding the potential of such small molecules in tuning the G-quadruplex bioactivity and G-quadeuplex-based sensor development.