Malina Jaroslav, Hannon Michael J, Brabec Viktor
Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i. Kralovopolska 135, 61265 Brno, Czech Republic.
Chemistry. 2008;14(33):10408-14. doi: 10.1002/chem.200801364.
Metallosupramolecular chemistry was used to design a new class of synthetic agents, namely, tetracationic supramolecular cylinders, that bind strongly and noncovalently in the major groove of DNA. To gain additional information on interactions of the cylinders with DNA we explored DNA unwinding and sequence-specific binding properties, as well as DNA photonuclease activity of ruthenium(II) metallosupramolecular cylinder Ru(2)L(3), where L is a bis-pyridylimine ligand. We found that Ru(2)L(3) unwinds negatively supercoiled plasmid DNA and exhibits binding preference to regular alternating purine-pyrimidine sequences in a similar way to the Fe(2)L(3) analogue. Photocleavage studies showed that, unlike Fe(2)L(3), Ru(2)L(3) induces single-strand breaks on irradiation by visible and UVA light and cleaves DNA mainly at guanine residues contained preferentially in regularly alternating purine-pyrimidine nucleotides. As Ru(2)L(3) binds and cleaves DNA in a sequence-dependent manner, it may provide a useful tool for basic and applied biology, such as for controlled manipulation of the genome.
金属超分子化学被用于设计一类新型合成试剂，即四阳离子超分子圆柱体，它们能在DNA的大沟中进行强非共价结合。为了获取更多关于这些圆柱体与DNA相互作用的信息，我们研究了Ru(2)L(3)（其中L为双吡啶亚胺配体）的DNA解旋、序列特异性结合特性以及DNA光核酸酶活性。我们发现，Ru(2)L(3)能解开负超螺旋质粒DNA，并且与Fe(2)L(3)类似物一样，对规则交替的嘌呤 - 嘧啶序列表现出结合偏好。光切割研究表明，与Fe(2)L(3)不同，Ru(2)L(3)在可见光和紫外光A照射下会诱导单链断裂，并且主要在规则交替的嘌呤 - 嘧啶核苷酸中优先含有的鸟嘌呤残基处切割DNA。由于Ru(2)L(3)以序列依赖的方式结合和切割DNA，它可能为基础生物学和应用生物学提供一个有用的工具，例如用于对基因组的可控操作。
