Department of Medicine, Clinical Translational Research Building, University of Louisville, 505 Hancock Street, Louisville, Kentucky 40202, USA.
J Am Chem Soc. 2010 Dec 8;132(48):17105-7. doi: 10.1021/ja105259m. Epub 2010 Nov 18.
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)3GGG)) 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.
影响 G-四链体形成序列构象和稳定性的因素仍知之甚少。在这里，我们使用圆二色性、NMR 和热力学相结合的方法，证明了在含有 K(+)和 Na(+)的溶液中，溶剂对人类端粒序列 d(A(GGGTTA)3GGG))构象和稳定性的影响。以前曾有人用分子拥挤的论点来表明平行四链体形式可能具有生物学相关性。然而，之前使用的小分子溶剂 PEG 200 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(+)溶液中观察到类似的构象转变。此外，NMR 分析表明，所得结构包含非反式鸟嘌呤糖苷扭转角，这表明乙腈中的构象与全平行晶体结构不同，尽管 CD 光谱显示为平行类型。
