原子力显微镜单分子力谱技术在G四链体研究中的应用

端粒在细胞的生理病理过程中起到至关重要的作用。端粒末端有一段富含鸟嘌呤（G）的单链DNA重复序列，该序列在单价金属离子如Na+或K+作用下可以折叠形成G-四链体结构，这一结构不能被端粒酶延长，从而抑制了端粒酶的活性，因此成为了潜在的抗癌药物作用靶点。目前，寻找能够稳定DNAG-四联体结构形成的小分子配体成为了许多抗癌药物设计的新思路。研究这些小分子配体与G-四链体的作用强度对高效抗癌药物的筛选尤为重要。单分子力谱技术可以直接观察到小分子配体与G-四链体间的相互作用。本文主要综述了原子力显微镜单分子力谱技术在G-四链体及其与小分子配体相互作用的研究进展，并对单分子力谱技术在G-四链体中的应用和发展趋势进行了总结和展望。

Application of atomic force microscopy-based single molecule force spectroscopy inG-quadruplex studies

Telomere plays a crucial role in the physiological and pathological processes of cells. At the end of the telomere, thesingle-stranded DNA repeat sequence rich in guanine (G) folds in the presence of monovalent metal ions such as Na+ or K+ toform a G-quadruplex structure. This structure can not be extended by telomerase and inhibits the activity of telomerase, thusbecoming a potential anticancer target. Stabilizing the formation of DNA G-quadruplex structures by small molecule ligandshas become a new strategy for designing many anticancer drugs, and studying the interaction strength of these small moleculeligands with G-quadruplex is thus of particular importance for screening highly effective anticancer drugs. Single moleculeforce spectroscopy enables direct measurement of the interaction between small molecule ligands and G-quadruplexes. Thisreview highlights the advances of single-molecule force spectroscopy based on atomic force microscopy in the study of the Gquadruplex structure and its interaction with small molecule ligands, and summarizes the application and development trendof single molecule force spectrum technology in G quadruplex.