Mori Keita, Takezawa Yusuke, Shionoya Mitsuhiko
Department of Chemistry, Graduate School of Science, The University of Tokyo 7-3-1 Hongo, Bunkyo-ku Tokyo 113-0033 Japan
Chem Sci. 2023 Jan 3;14(5):1082-1088. doi: 10.1039/d2sc06534g. eCollection 2023 Feb 1.
Dynamic control of DNA assembly by external stimuli has received increasing attention in recent years. Dynamic ligand exchange in metal complexes can be a central element in the structural and functional transformation of DNA assemblies. In this study, ,-dicarboxymethyl-5-aminouracil (dcaU) nucleoside with an iminodiacetic acid (IDA) ligand at the 5-position of the uracil base has been developed as a bifacial nucleoside that can form both hydrogen-bonded and metal-mediated base pairs. Metal complexation study of dcaU nucleosides revealed their ability to form a 2:1 complex with a Gd ion at the monomeric level. The characteristics of base pairing of dcaU nucleosides were then examined inside DNA duplexes. The results revealed that the formation of the metal-mediated dcaU-Gd-dcaU pair significantly stabilized the DNA duplex containing one dcaU-dcaU mismatch (Δ = +16.1 °C). In contrast, a duplex containing a hydrogen-bonded dcaU-A pair was destabilized in the presence of Gd (Δ = -3.5 °C). The Gd-dependent base pairing of dcaU bases was applied to control the hybridization preference of DNA in response to metal ions. The hybridization partner of a dcaU-containing strand was reversibly exchanged by the addition and removal of Gd ions. Since the incorporation of a single dcaU base can switch the hybridization behavior of DNA, the bifacial dcaU base would be a versatile building block for imparting metal responsiveness to DNA assemblies, allowing the rational design of dynamic DNA systems.
近年来，外部刺激对DNA组装的动态控制受到了越来越多的关注。金属配合物中的动态配体交换可能是DNA组装体结构和功能转变的核心要素。在本研究中，已开发出在尿嘧啶碱基5位带有亚氨基二乙酸（IDA）配体的β,β-二羧甲基-5-氨基尿嘧啶（dcaU）核苷，作为一种既能形成氢键又能形成金属介导碱基对的双面核苷。dcaU核苷的金属络合研究表明，它们在单体水平上能够与钆离子形成2:1的络合物。然后在DNA双链体内部研究了dcaU核苷的碱基配对特性。结果表明，金属介导的dcaU-Gd-dcaU对的形成显著稳定了含有一个dcaU-dcaU错配的DNA双链体（ΔTm = +16.1 °C）。相反，含有氢键连接的dcaU-A对的双链体在钆存在下不稳定（ΔTm = -3.5 °C）。dcaU碱基的钆依赖性碱基配对被用于控制DNA对金属离子响应的杂交偏好。通过添加和去除钆离子，可逆地交换了含dcaU链的杂交伴侣。由于单个dcaU碱基的掺入可以改变DNA的杂交行为，双面dcaU碱基将是赋予DNA组装体金属响应性的通用构件，从而实现动态DNA系统的合理设计。
