【作者】 宋迪； 姚翔梓； 秦廷萧； 刘坤辉； 苏红梅；

【Author】 Di Song;Xiangzi Yao;Tingxiao Qin;Kunhui Liu;Hongmei Su;Institute of Chemistry, Chinese Academy of Sciences;College of Chemistry, Beijing Normal University;

【机构】 中国科学院化学研究所； 北京师范大学化学学院；

【摘要】 G-四链体是DNA的二级结构,形成于端粒的末端。它可以抑制端粒酶的活性,所以被认为是癌症治疗的靶点。配体小分子,如卟啉及其衍生物,可以进一步稳定G-四链体,干扰端粒的复制,有望成为新型的抗癌药物。本文聚焦于配体锌卟啉,主要研究它与重要的G-四链体之间的相互作用模式,以及结合比。我们利用锌卟啉三重态敏感于微环境的特点,一次测量即得到锌卟啉分子与G-四链体的两种共存的结合模式。并通过改变摩尔比,得到锌卟啉分子与所研究的G-四链体的结合比。这为设计和筛选新型抗癌药物提供了有价值的信息。更多还原

【Abstract】 G-quadruplexes are tetrastranded helical structures arising from the self-assembly of specific guanine-rich DNA sequences, which have ability to inhibit the activity of telomerase that is activated in most cancer cells, thereby G-quadruplexes can act as tumor-selective targets for cancer treatment. A large number of small molecules(ligands) can stabilize G-quadruplexes, interfering with telomere replication and thus becoming new anticancer agents. To design and synthesize efficient ligands, understanding for G-quadruplex-interactions of ligand is required. This work focuses on the binding between Zn-TMPyP 4 and four important telomeric G-quadruplexes. Utilizing the feature of Zn-TMPyP 4 whose triplet decay dynamics are highly sensitive to its local environment, we performed transient spectroscopy measurements. Two lifetimes are observed in an assay, which are associated with two coexist binding modes. With variations of molar ratios, binding stoichiometries for four binary systems are also obtained. These results are value for design of highly efficient quadruplex ligands.更多还原