Department of Chemistry, Faculty of Science, University of Kragujevac, R. Domanovića 12, 34000, Kragujevac, Serbia.
Institute of Chemistry Technology and Metallurgy, National Institute of the Republic of Serbia, University of Belgrade, Njegoševa 12, 11000, Belgrade, Serbia.
J Biol Inorg Chem. 2022 Feb;27(1):65-79. doi: 10.1007/s00775-021-01911-6. Epub 2021 Oct 29.
The mechanism of action of most approved drugs in use today is based on their binding to specific proteins or DNA. One of the achievements of this research is a new perspective for recognition of binding modes to DNA by monitoring of changes in measured and stoichiometric values of absorbance at 260 nm. UV-Vis and IR spectroscopy, gel electrophoresis and docking study were used for investigation of binding properties of three dinuclear platinum(II) complexes containing different pyridine-based bridging ligands, [{Pt(en)Cl}(μ-4,4'-bipy)]Cl·2HO (Pt1), [{Pt(en)Cl}(μ-bpa)]Cl·4HO (Pt2) and [{Pt(en)Cl}(μ-bpe)]Cl·4HO (Pt3) to DNA (4,4'-bipy, bpa and bpe are 4,4'-bipyridine, 1,2-bis(4-pyridyl)ethane and 1,2-bis(4-pyridyl)ethene, respectively). In contrast to the system with well-known intercalated ligand (EtBr), covalently bound ligand (cis-Pt) and with minor groove binder (Hoechst 33258), which do not have significant differences in measured and stoichiometric values, the most pronounced deviations are recorded for two dinuclear platinum(II) complexes (Pt1 and Pt2), as a consequence of complex binding to the phosphate backbone and bending of DNA helix. The hydrolysis of complexes and changes in DNA conformation were also analysed as phenomena that may have an impact on the changes in absorbance.
目前大多数已批准药物的作用机制基于它们与特定蛋白质或 DNA 的结合。这项研究的成果之一是，通过监测在 260nm 处吸光度的测量值和化学计量值的变化，为识别与 DNA 结合模式提供了新的视角。使用 UV-Vis 和 IR 光谱、凝胶电泳和对接研究来研究三种包含不同基于吡啶的桥联配体的双核铂(II)配合物[{Pt(en)Cl}(μ-4,4'-bipy)]Cl·2HO(Pt1)、[{Pt(en)Cl}(μ-bpa)]Cl·4HO(Pt2)和[{Pt(en)Cl}(μ-bpe)]Cl·4HO(Pt3)与 DNA（4,4'-bipy、bpa 和 bpe 分别为 4,4'-联吡啶、1,2-双(4-吡啶基)乙烷和 1,2-双(4-吡啶基)乙烯）的结合特性。与具有已知嵌入配体（EtBr）、共价键合配体（顺式-Pt）和小沟结合剂（Hoechst 33258）的体系不同，这些体系在测量值和化学计量值上没有显著差异，对于两种双核铂(II)配合物（Pt1 和 Pt2），记录到最明显的偏差，这是由于复合物与磷酸骨架结合以及 DNA 螺旋的弯曲。还分析了配合物的水解和 DNA 构象的变化，这些变化可能对吸光度的变化有影响。
