Development of Metal Complexes with Functions of Recognition and Tranformation of Nucleic Acids for Control of Gene Expression

We previously demonstrated that Zn^<II>-cyclen complexes bind selecively and reversibly to thymine （or uracil） base in aqueous solution at physiological pH.These zinc complexes also lowered the melting temperatures of double-stranded poly （A） ·Poly （U） and poly （DA） ·poly （dT）， indicating the double-stranded structures of the polynucleotides are destabilized by the strong interaction between these complexes and thymine （or uracil） bases。我们已经进一步研究了金属复合体和DNA双lexes之间的相互作用，这些序列经常在转录调节域中看到。例如， Zn^<II>-cyclen复合体用一组腺病毒TATA盒来破坏寡体DNA的双链结构，并以相对较低的熔融温度（T_m）依赖于锌复合体的集中和溶液的pH值。在对比度、Ni^<II>-和Cu^<II>-cyclen复合体中降低了T_m。在添加中，由于创造人工DNA作为功能化材料的目的，我们将合成一种新型核苷酸，以携带苯二胺亚单元进行金属协调。当氢键入是在自然DNA中形成双螺旋体的主要驱动力之一，而这种核酸酶可能是在金属协调中形成双螺旋体的人工DNA，在任何金属可以与螺旋体对齐的情况下。Hence，这些金属对齐的结构在DNA中有可能应用于分子电线、光学设备和药物等。

We previously demonstrated that Zn^<II>-cyclen complexes bind selecively and reversibly to thymine (or uracil) base in aqueous solution at physiological pH.These zinc complexes also lowered the melting temperatures of double-stranded poly (A) ・Poly (U) and poly (dA) ・poly (dT), indicating that the double-stranded structures of the polynucleotides are destabilized by the strong interaction between these complexes and thymine (or uracil) bases. We have further studied the interactions between metal complexes and DNA duplexes containing AT-rich sequences which are often seen in transcriptional regulatory domains. For example, Zn^<II>-cyclen complex destabilized the double-stranded structure of oligomeric DNAs with a sequence of adenovirus TATA-box, and consequently lowered the melting temperature (T_m) depending on the concentration of the zinc complex and the solution pH.In contrast, Ni^<II>-and Cu^<II>-cyclen complexes raised the T_m. In addition, for the purpose of creating artificial DNAs as functionalized materials, we synthesized a novel nucleoside bearing a phenylenediamine subunit for metal coordination. While hydrogen donding is one of the primary driving forces to form double helixes in natural DNA,the artificial DNAs with this nucleobase are expected to form double stranded structures by metal coordination, in which metals may align along the helix axis. Hence, these metal aligned structures in the DNA have possibility of application to molecular wire, optical devices, and drugs, etc.