Dipartimento di Fisica e Geologia, Università di Perugia, Via Pascoli, 06123 Perugia, Italy.
Niels Bohr Institute, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen, Denmark.
J Phys Chem Lett. 2021 Aug 26;12(33):8096-8102. doi: 10.1021/acs.jpclett.1c01840. Epub 2021 Aug 18.
Nucleic acid sequences rich in guanines can organize into noncanonical DNA G-quadruplexes (G4s) of variable size. The design of small molecules stabilizing the structure of G4s is a rapidly growing area for the development of novel anticancer therapeutic strategies and bottom-up nanotechnologies. Among a multitude of binders, porphyrins are very attractive due to their light activation that can make them valuable conformational regulators of G4s. Here, a structure-based strategy, integrating complementary probes, is employed to study the interaction between TMPyP4 porphyrin and a 22-base human telomeric sequence (Tel22) before and after irradiation with blue light. Porphyrin binding is discovered to promote Tel22 dimerization, while light irradiation of the Tel22-TMPyP4 complex controls dimer fraction. Such a change in quaternary structure is found to be strictly correlated with modifications at the secondary structure level, thus providing an unprecedented link between the degree of dimerization and the underlying conformational changes in G4s.
富含鸟嘌呤的核酸序列可以组织成大小可变的非经典 DNA G-四链体（G4s）。设计稳定 G4 结构的小分子是开发新型抗癌治疗策略和自下而上纳米技术的快速发展领域。在众多结合物中，卟啉因其光激活而非常有吸引力，这可以使它们成为 G4s 的有价值的构象调节剂。在这里，采用一种基于结构的策略，整合互补探针，研究了 TMPyP4 卟啉与人类端粒序列（Tel22）在蓝光照射前后的相互作用。发现卟啉结合促进了 Tel22 的二聚化，而 Tel22-TMPyP4 复合物的光照射控制二聚体分数。这种四级结构的变化被发现与二级结构水平的修饰严格相关，从而在二聚化程度和 G4s 中的构象变化之间提供了前所未有的联系。
