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

We previously demonstrated that Zn^&lt；II&gt；-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 strong interaction weetthes.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^&lt；II&gt；-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^&lt；II&gt；-and Cu^&lt；II&gt；-cyclen complexes raised the T_m.In addition，for the purpose of creating ificial NAial as funized the double-strating，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.

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.