1997 Fiscal Year Final Research Report Summary

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

Research Project

Project/Area Number	08457623
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Research Field	医薬分子機能学
Research Institution	Okazaki National Research Institutes
Principal Investigator	SHIONOYA Mitsuhiko Institute for Molecular Science, Professor, 分子科学研究所, 教授 (60187333)
Co-Investigator(Kenkyū-buntansha)	TANAKA Kentaro Institute for Molecular Science, Research Assistant, 分子科学研究所, 助手 (40281589)
Project Period (FY)	1996 – 1997
Keywords	Control of Gene Expression / Metal Complexes / Coodination Chemistry / Nucleic Acid
Research Abstract	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.