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Metal-dependent base pairing of bifacial iminodiacetic acid-modified uracil bases for switching DNA hybridization partner
Chemical Science ( IF 7.6 ) Pub Date : 2023-01-03 , DOI: 10.1039/d2sc06534g
Keita Mori 1 , Yusuke Takezawa 1 , Mitsuhiko Shionoya 1
Affiliation  

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, N,N-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 GdIII 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–GdIIIdcaU pair significantly stabilized the DNA duplex containing one dcaUdcaU mismatch (ΔTm = +16.1 °C). In contrast, a duplex containing a hydrogen-bonded dcaU–A pair was destabilized in the presence of GdIIITm = −3.5 °C). The GdIII-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 GdIII 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.

中文翻译:

用于切换 DNA 杂交伴侣的双面亚氨基二乙酸修饰尿嘧啶碱基的金属依赖性碱基配对

近年来,外部刺激对DNA组装的动态控制受到越来越多的关注。金属配合物中的动态配体交换可能是 DNA 组装结构和功能转化的核心要素。在这项研究中,N , N-二羧甲基-5-氨基尿嘧啶 ( dcaU ) 核苷在尿嘧啶碱基的 5 位上具有亚氨基二乙酸 (IDA) 配体,已被开发为一种双面核苷,可以形成氢键和金属键合-介导的碱基对。dcaU核苷的金属络合研究揭示了它们能够在单体水平上与 Gd III离子形成 2:1 络合物。然后检查 DNA 双链体内部dcaU核苷的碱基配对特征。结果表明,金属介导的dcaU –Gd IIIdcaU对的形成显着稳定了含有一个dcaUdcaU错配的DNA 双链体(Δ T m = +16.1 °C)。相比之下,含有氢键dcaU –A 对的双链体在 Gd III存在下不稳定(Δ T m = -3.5 °C)。应用dcaU碱基的Gd III依赖性碱基配对来控制 DNA 响应金属离子的杂交偏好。通过添加和去除 Gd III离子,可逆地交换含dcaU链的杂交配偶体。由于单个dcaU碱基的掺入可以改变 DNA 的杂交行为,因此双面dcaU碱基将成为赋予 DNA 组件金属响应性的多功能构建块,从而允许动态 DNA 系统的合理设计。
更新日期:2023-01-03
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