G-Quadruplex Induction by the Hairpin Pyrrole–Imidazole Polyamide Dimer,Biochemistry

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G-Quadruplex Induction by the Hairpin Pyrrole–Imidazole Polyamide Dimer
Biochemistry ( IF 2.9 ) Pub Date : 2017-12-15 00:00:00 , DOI: 10.1021/acs.biochem.7b01059
Shunsuke Obata ₁ , Sefan Asamitsu ₁ , Kaori Hashiya ₁ , Toshikazu Bando ₁ , Hiroshi Sugiyama _{1,

2}

Affiliation

The G-quadruplex (G4) is one type of higher-order structure of nucleic acids and is thought to play important roles in various biological events such as regulation of transcription and inhibition of DNA replication. Pyrrole–imidazole polyamides (PIPs) are programmable small molecules that can sequence-specifically bind with high affinity to the minor groove of double-stranded DNA (dsDNA). Herein, we designed head-to-head hairpin PIP dimers and their target dsDNA in a model G4-forming sequence. Using an electrophoresis mobility shift assay and transcription arrest assay, we found that PIP dimers could induce the structural change to G4 DNA from dsDNA through the recognition by one PIP dimer molecule of two duplex-binding sites flanking both ends of the G4-forming sequence. This induction ability was dependent on linker length. This is the first study to induce G4 formation using PIPs, which are known to be dsDNA binders. The results reported here suggest that selective G4 induction in native sequences may be achieved with PIP dimers by applying the same design strategy.

中文翻译：

发夹状吡咯-咪唑聚酰胺二聚体引起的G-四链体诱导

G-四链体（G4）是一种核酸的高阶结构，被认为在各种生物事件（例如转录调控和DNA复制抑制）中起着重要作用。吡咯-咪唑聚酰胺（PIP）是可编程的小分子，可以高特异性地与双链DNA（dsDNA）的小沟序列特异性结合。在本文中，我们以模型G4形成序列设计了头对头发夹式PIP二聚体及其靶标dsDNA。使用电泳迁移率迁移测定和转录停滞测定，我们发现PIP二聚体可通过一个PIP二聚体分子识别位于G4形成序列两端的两个双链体结合位点来诱导dsDNA从GDNA到G4 DNA的结构变化。该诱导能力取决于接头长度。这是第一个使用PIP诱导G4形成的研究，PIP是dsDNA结合物。此处报道的结果表明，通过应用相同的设计策略，可以使用PIP二聚体实现天然序列中的选择性G4诱导。

更新日期：2017-12-15

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