A Photoresponsive Stiff-Stilbene Ligand Fuels the Reversible Unfolding of G-Quadruplex DNA

A Photoresponsive Stiff-Stilbene Ligand Fuels the Reversible Unfolding of G-Quadruplex DNA
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光响应性二苯乙烯配体促进 G-四链体 DNA 的可逆展开

DOI:
10.1002/ange.201900740
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发表时间:
2019
期刊:
影响因子:
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通讯作者:
O'Hagan M
O'Hagan M
中科院分区:
--
文献类型:
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作者:
O'Hagan M

文献摘要

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G-四链(G4)DNA结构的多态性质表明了在纳米设备中的一系列潜在应用,并为在生物环境中控制G4提供了机会。光具有很高的时空精确度,是一种很有吸引力的寡核苷酸结构调控手段。然而,令人惊讶的是,很少有人关注G4配体的开发,这些配体可以光调节G4折叠。我们报道了一种由二苯乙烯类化合物衍生的新的G4结合化学型。然而,令人惊讶的是,虽然该配体诱导了人端粒DNA的钾形式的高度稳定,但它导致了相同的G4序列在钠缓冲中的展开。这种效应可以根据需要通过400 nm的光照射来逆转,通过光氧化使配体失活。通过以耐光性配体为燃料,G4DNA的构象发生了五次转换。
The polymorphic nature of G‐quadruplex (G4) DNA structures points to a range of potential applications in nanodevices and an opportunity to control G4 in biological settings. Light is an attractive means for the regulation of oligonucleotide structure as it can be delivered with high spatiotemporal precision. However, surprisingly little attention has been devoted towards the development of ligands for G4 that allow photoregulation of G4 folding. We report a novel G4‐binding chemotype derived from stiff‐stilbene. Surprisingly however, whilst the ligand induces high stabilization in the potassium form of human telomeric DNA, it causes the unfolding of the same G4 sequence in sodium buffer. This effect can be reversed on demand by irradiation with 400 nm light through deactivation of the ligand by photo‐oxidation. By fuelling the system with the photolabile ligand, the conformation of G4 DNA was switched five times.