Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
J Biol Inorg Chem. 2010 Jun;15(5):629-39. doi: 10.1007/s00775-010-0630-5. Epub 2010 Feb 26.
Modified oligonucleotides are showing potential for multiple applications, including drug design, nanoscale building blocks, and biosensors. In an effort to expand the functionality available to DNA, we have placed chelating ligands directly into the backbone of DNA. Between one and three nucleosides were replaced with 2,2'-bipyridine phosphates in 23-mer duplexes of DNA. An array of metal ions were added (Fe(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), and Pt(2+)) and the influences on duplex stability were examined by melting temperature studies. Titrations and UV-vis absorption spectroscopy were used to provide insights into the nature of the metal complexes formed. We found that Ni(2+) binding to 2,2'-bipyridine typically provided the greatest increase in duplex stability relative to the other metal ions examined. For example, addition of Ni(2+) to one 2,2'-bipyridine-DNA duplex increased the melting temperature by 13 degrees C, from 65.0 +/- 0.3 to 78.4 +/- 0.9 degrees C. These studies show that metal ions and backbone ligands can be used to regulate DNA structure and stability.
修饰后的寡核苷酸在多个领域具有应用潜力，包括药物设计、纳米尺度构建块和生物传感器。为了拓展 DNA 的功能，我们将螯合剂直接引入 DNA 的骨架中。在 23 个碱基对的 DNA 双链体中，将 1 到 3 个核苷酸替换为 2,2'-联吡啶磷酸盐。我们添加了一系列金属离子（Fe(2+)、Co(2+)、Ni(2+)、Cu(2+)、Zn(2+)和 Pt(2+)），并通过熔点研究来研究其对双链体稳定性的影响。滴定和紫外可见吸收光谱用于提供有关形成的金属配合物性质的见解。我们发现，与其他研究的金属离子相比，Ni(2+)与 2,2'-联吡啶的结合通常能提供最大的双链体稳定性增加。例如，向一个 2,2'-联吡啶-DNA 双链体中添加 Ni(2+)可将熔点提高 13°C，从 65.0 +/- 0.3°C 增加到 78.4 +/- 0.9°C。这些研究表明，金属离子和骨架配体可用于调节 DNA 结构和稳定性。
