The Interaction of Cyclic Naphthalene Diimide with G-Quadruplex under Molecular Crowding Condition
The Interaction of Cyclic Naphthalene Diimide with G-Quadruplex under Molecular Crowding Condition
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DOI：
10.3390/molecules25030668
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发表时间：
2020-02
期刊：
影响因子：
4.6
通讯作者：
Tingting Zou;Shinobu Sato;Rui Yasukawa;Ryusuke Takeuchi;Shunsuke Ozaki;S. Fujii;S. Takenaka
中科院分区：
文献类型：
--
作者：
Tingting Zou;Shinobu Sato;Rui Yasukawa;Ryusuke Takeuchi;Shunsuke Ozaki;S. Fujii;S. Takenaka
G-四链体特异性靶向分子，又称G4配体，因其识别和稳定G-四链体的能力以及在生物调节方面的巨大潜力而受到越来越多的关注。然而，识别G-四链的G4配体通常是在稀释性条件下研究的，这可能会在细胞拥挤的环境中受到干扰。在这里，我们设计并合成了几个新的环状萘二亚胺(CNDI)衍生物，并在分子拥挤条件下(40%v/v聚乙二醇200)研究了它们与G-四链体的相互作用，以模拟细胞条件。结果表明，在分子拥挤条件下，cNDI衍生物仍然能够识别和稳定基于圆二色谱的G-四链结构。通过等温滴定量热法和UV-Vis吸收光谱测定，结合亲和力略有下降，但仍较高。更有趣的是，在阳离子缺乏的分子拥挤条件下，cNDI衍生物被观察到优先诱导端粒序列形成杂交的G-四链。
G-quadruplex specific targeting molecules, also termed as G4 ligands, are attracting increasing attention for their ability to recognize and stabilize G-quadruplex and high potentiality for biological regulation. However, G4 ligands recognizing G-quadruplex were generally investigated within a dilute condition, which might be interfered with under a cellular crowding environment. Here, we designed and synthesized several new cyclic naphthalene diimide (cNDI) derivatives, and investigated their interaction with G-quadruplex under molecular crowding condition (40% v/v polyethylene glycol (PEG)200) to mimic the cellular condition. The results indicated that, under molecular crowding conditions, cNDI derivatives were still able to recognize and stabilize G-quadruplex structures based on circular dichroism measurement. The binding affinities were slightly decreased but still comparatively high upon determination by isothermal titration calorimetry and UV-vis absorbance spectroscopy. More interestingly, cNDI derivatives were observed with preference to induce a telomere sequence to form a hybrid G-quadruplex under cation-deficient molecular crowding conditions.