School of Chemistry, University of Bristol, Cantock's Close, BS8 1TS, UK.
Instituto de Parasitología y Biomedicina "López Neyra", Consejo Superior de Investigaciones Científicas (CSIC), PTS Granada, Avenida del Conocimiento 17, 18016, Armilla, Granada, Spain.
Angew Chem Int Ed Engl. 2019 Mar 22;58(13):4334-4338. doi: 10.1002/anie.201900740. Epub 2019 Feb 20.
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.
G-四链体 (G4) DNA 结构的多态性表明其在纳米器件中有广泛的潜在应用，并为控制生物环境中的 G4 提供了机会。光作为调节寡核苷酸结构的一种有吸引力的手段，因为它可以具有高精度的时空传递。然而，令人惊讶的是，很少有研究致力于开发允许 G4 折叠光调控的 G4 配体。我们报告了一种新型的源自刚性联苯的 G4 结合化学型。然而令人惊讶的是，虽然该配体在钾形式的人类端粒 DNA 中诱导了高度稳定，但它会导致在钠离子缓冲液中展开相同的 G4 序列。通过用 400nm 光照射进行光氧化失活，该配体可按需逆转此效应。通过用光不稳定配体为系统供能，G4 DNA 的构象被切换了五次。
