Department of Chemistry, Imperial College London, London, SW7 2AZ, UK.
Universidad de Burgos, Departamento de Química, 09001, Burgos, Spain.
Chemistry. 2018 Aug 9;24(45):11785-11794. doi: 10.1002/chem.201802248. Epub 2018 Jul 16.
The proposed in vivo formation of G-quadruplex DNA (G4 DNA) in promoter regions of oncogenes and in telomeres has prompted the development of small molecules with high affinity and selectivity for these structures. Herein we report the synthesis of a new di-substituted bipyridine ligand and the corresponding complexes with Ni and VO . Both these new complexes have been characterized spectroscopically and by X-ray crystallography. Detailed DNA binding studies of these two complexes, together with three previously reported metal salphen complexes, are presented. Using FRET melting assays, the binding affinity and selectivity of the five metal complexes against six different G4 DNA structures as well as a duplex DNA have been determined. In addition, we present detailed ITC and UV/Vis studies to characterize the interaction of the complexes with human telomeric G4 DNA. Finally, we show via a polymerase stop assay that these complexes are able to stabilize a G4 DNA structure (from the c-Myc oncogene promoter) and halt the activity of Taq polymerase.
在癌基因启动子区和端粒中存在 G-四链体 DNA（G4 DNA）的体内形成这一现象，促使人们开发出了对这些结构具有高亲和力和选择性的小分子。在此，我们报告了一种新的二取代联吡啶配体及其相应的 Ni 和 VO 配合物的合成。这两种新配合物均通过光谱法和 X 射线晶体学进行了表征。详细介绍了这两种配合物以及之前报道的三种金属 salphen 配合物的 DNA 结合研究。通过荧光共振能量转移（FRET）熔融实验，测定了这 5 种金属配合物对 6 种不同 G4 DNA 结构以及双链 DNA 的结合亲和力和选择性。此外，我们通过详细的 ITC 和 UV/Vis 研究来表征配合物与人类端粒 G4 DNA 的相互作用。最后，通过聚合酶停止实验表明，这些配合物能够稳定 G4 DNA 结构（来自 c-Myc 癌基因启动子）并阻止 Taq 聚合酶的活性。
