Szumilak Marta, Merecz Anna, Strek Malgorzata, Stanczak Andrzej, Inglot Tadeusz W, Karwowski Boleslaw T
Department of Hospital Pharmacy, Faculty of Pharmacy, Medical University of Lodz, 1 Muszynskiego Street, 90-151 Lodz, Poland.
Food Science Department, Faculty of Pharmacy, Medical University of Lodz, 1 Muszynskiego Street, 90-151 Lodz, Poland.
Int J Mol Sci. 2016 Sep 19;17(9):1560. doi: 10.3390/ijms17091560.
The interaction of polyamine conjugates with DNA double helix has been studied. Binding properties were examined by ethidium bromide (EtBr) displacement and DNA unwinding/topoisomerase I/II (Topo I/II) activity assays, as well as dsDNA thermal stability studies and circular dichroism spectroscopy. Genotoxicity of the compounds was estimated by a comet assay. It has been shown that only compound can interact with dsDNA via an intercalative binding mode as it displaced EtBr from the dsDNA-dye complex, with = 4.26 × 10⁶ M; caused an increase in melting temperature; changed the circular dichroism spectrum of dsDNA; converted relaxed plasmid DNA into a supercoiled molecule in the presence of Topo I and reduced the amount of short oligonucleotide fragments in the comet tail. Furthermore, preliminary theoretical study has shown that interaction of the discussed compounds with dsDNA depends on molecule linker length and charge distribution over terminal aromatic chromophores.
已对多胺缀合物与DNA双螺旋的相互作用进行了研究。通过溴化乙锭（EtBr）置换、DNA解旋/拓扑异构酶I/II（Topo I/II）活性测定、双链DNA热稳定性研究以及圆二色光谱法来检测结合特性。通过彗星试验评估化合物的遗传毒性。结果表明，只有化合物能够通过插入结合模式与双链DNA相互作用，因为它能从双链DNA - 染料复合物中置换出EtBr，解离常数Kd = 4.26 × 10⁶ M；导致解链温度升高；改变双链DNA的圆二色光谱；在Topo I存在的情况下将松弛的质粒DNA转化为超螺旋分子，并减少彗星尾中短寡核苷酸片段的数量。此外，初步理论研究表明，所讨论的化合物与双链DNA的相互作用取决于分子连接体长度和末端芳香发色团上的电荷分布。
