Metal ion-directed dynamic splicing of DNA through global conformational change by intramolecular complexation
Metal ion-directed dynamic splicing of DNA through global conformational change by intramolecular complexation
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DOI：
10.1038/ncomms7640
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发表时间：
2015-04-01
影响因子：
16.6
通讯作者：
Kitamura, Yusuke
中科院分区：
文献类型：
--
作者：
Ihara, Toshihiro;Ohura, Hiroyuki;Kitamura, Yusuke
经过化学工程改造的 DNA（其中整体构象可以根据特定刺激进行调节）本身可以是变构功能性 DNA，也可以作为功能性核酸（例如 DNAzyme 和适体）的调节剂。在这里，我们证明DNA主链中构建的两个三联吡啶与二价过渡金属离子形成稳定的分子内1:2复合物[M(terpy)(2)](2+)。络合后，DNA缀合物采用Omega形结构，其中位于三联吡啶外部的两个远端序列彼此连接，形成具有特定结构或序列的连续片段。这种 DNA 结构由局部金属络合事件全局控制，可以根据一般配位化学合理设计。该方法被视为金属离子定向动态序列编辑或DNA剪接。因此，具有过氧化物酶样活性的 DNAzyme 可以通过基于 Omega 基序的序列编辑技术受到多种过渡金属离子的调节。
Chemically engineered DNAs-in which global conformation can be modulated in response to specific stimuli-could be allosteric functional DNAs themselves or work as a modulator of the functional nucleic acids such as DNAzymes and aptamers. Here, we show that two terpyridines built in the DNA backbone form a stable intramolecular 1:2 complex, [M(terpy)(2)](2+), with divalent transition metal ions. Upon complexation, the DNA conjugates adopt a Omega-shape structure, in which two distal sequences located outside the terpyridines connect with each other to form a continuous segment with a specific structure or sequence. Such a DNA structure is globally controlled by local metal complexation events that can be rationally designed based on general coordination chemistry. This method is regarded as metal ion-directed dynamic sequence edition or DNA splicing. DNAzymes with peroxidase-like activity can thus be regulated by several transition metal ions through sequence edition techniques based on the Omega-motif.