【摘要】 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DNA G-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。更多还原

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