Hydration Is a Major Determinant of the G-Quadruplex Stability and Conformation of the Human Telomere 3′ Sequence of d(AG3(TTAG3)3)
Hydration Is a Major Determinant of the G-Quadruplex Stability and Conformation of the Human Telomere 3′ Sequence of d(AG3(TTAG3)3)
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DOI：
10.1021/ja105259m
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发表时间：
2010-12-08
影响因子：
15
通讯作者：
Trent, John O.
中科院分区：
文献类型：
--
作者：
Miller, M. Clarke;Buscaglia, Robert;Trent, John O.
决定G-四链形成序列的构象和稳定性的因素仍然知之甚少。在这里，我们用圆二色谱、核磁共振和热力学相结合的方法证明了共溶剂对人端粒序列d(A(GGGTTA)(3)GGG)在K+和Na+溶液中的构象和稳定性的影响。分子拥挤的论点以前曾被用来暗示平行的四链形式可能与生物学相关。然而，之前使用的小型助溶剂PEG200和400实际上是脱水剂。我们使用乙腈作为非氢键脱水剂；在K+溶液中也观察到了类似的构象转变。此外，核磁共振分析表明，所得到的结构含有非反鸟嘌呤糖基扭转角，这表明乙腈中存在的构象与全平行晶体结构并不相同，尽管假设为平行型CD谱。
The factors that determine the conformation and stability of G-quadruplex forming sequences remain poorly understood. Here we demonstrate the influence of cosolvents on the conformation and stability of the human telomeric sequence d(A(GGGTTA)(3)GGG)) in both K+ and Na+ containing solutions using a combination of circular dichroism, NMR, and thermodynamics. Molecular crowding arguments have previously been used to suggest that the parallel quadruplex form may be biologically relevant. However, the small cosolvents previously used, PEG 200 and 400, are actually dehydrating agents. We have used acetonitrile as a non-hydrogen-bonding dehydrating agent; similar conformational transitions were observed in K+ solution. Moreover, NMR analysis shows that the resulting structure contains non-anti guanine glycosyl torsion angles suggesting that The conformation present in acetonitrile is not identical to the all-parallel crystal structure, despite the supposed parallel type CD spectrum.