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

具有核酸识别和转化功能的金属配合物的开发用于控制基因表达

• 批准号: 08457623
• 负责人: SHIONOYA Mitsuhiko
• 金额: $ 4.61万
• 依托单位: Okazaki National Research Institutes
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457623/
• 关键词: Control of Gene Expression; Metal Complexes; Coodination Chemistry; Nucleic Acid; 遺伝子発現; 分子認識; 錯体合成; 転写調節領域; チミン塩基; 塩基対認識

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.

我们以前证明了Zn^<II>-cyclen复合物在生理pH的水溶液中选择性地可逆结合胸腺嘧啶（或尿嘧啶）碱基。这些锌复合物还降低了双链poly（A）·Poly（U）和poly（dA）·poly（dT）的解链温度，表明这些复合物与胸腺嘧啶（或尿嘧啶）碱基之间的强相互作用使多核苷酸的双链结构不稳定。我们进一步研究了金属配合物与含有富含AT序列的DNA双链体之间的相互作用，这些序列常见于转录调节结构域。例如，Zn^<II>-cyclen络合物使含有腺病毒TATA盒序列的寡聚DNA的双链结构不稳定，从而降低了熔解温度（Tm），这取决于锌络合物的浓度和溶液的pH值;相反，Ni^<II>-和Cu^<II>-cyclen络合物提高了Tm。此外，为了创造人工DNA作为功能化材料，我们合成了一种新型的核苷携带苯二胺亚基的金属配位。虽然供氢是天然DNA中形成双螺旋的主要驱动力之一，但具有该核碱基的人工DNA有望通过金属配位形成双链结构，其中金属可以沿着螺旋轴排列。因此，DNA中的这些金属排列结构有可能应用于分子导线、光学器件和药物等。