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

基本信息

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

项目摘要

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.

我们先前证明了Zn^<ii> - 循环复合物在物理pH的水溶液中选择性和可逆地与胸腺胺（或尿嘧啶）基础结合。这些锌配合物还降低了双链poly（a）・ poly（u）和poly（da）・ poly（dt）的熔融温度，这表明多核苷酸的双链结构因这些复合物与胸腺胺（或尿素（或尿尿）基础之间的强相互作用而破坏了稳定的稳定。我们进一步研究了金属络合物与含有富含高素质序列的DNA双链体之间的相互作用，这些序列通常在转录调节域中看到。例如，Zn^<ii> - 循环复合物通过一系列腺病毒tata-box的寡聚DNA的双链结构不稳定，因此，根据锌复合物的浓度和溶液pH。ni^<ii> -andsive thempsive thement ph。此外，为了创建人工DNA作为功能化材料，我们合成了一种新型的核外侧，其苯基二胺亚基用于金属配位。虽然donning是在天然DNA中形成双螺旋的主要驱动力之一，但具有该核基碱的人工DNA有望通过金属协调形成双链结构，其中金属可以沿着螺旋轴对齐。因此，DNA中的这些金属排列结构具有用于分子线，光学设备和药物等的潜力。