Dipartimento di Farmacia, Università di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
Dipartimento di Farmacia, Università di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
Biochimie. 2014 Apr;99:119-28. doi: 10.1016/j.biochi.2013.11.020. Epub 2013 Dec 4.
In a previous work we have demonstrated that the DNA sequence CGGTGGT folds into a higher order G-quadruplex structure (2Q), obtained by the 5'-5' stacking of two unusual G(:C):G(:C):G(:C):G(:C) planar octads belonging to two identical tetra-stranded parallel quadruplexes, when annealed in the presence of ammonium or potassium ions. In the present paper, we discuss the role played by the title nucleosides X and Y (where X and Y stand for A, C, G, or T) on the formation and stability of 2Q structures formed by the XGGYGGT oligodeoxynucleotides. We found that the above mentioned dimerization pathway is not peculiar to the CGGTGGT sequence, but is possible for all the remaining CGGYGGT sequences (with Y = A, C, or G). Furthermore, we have found that the TGGAGGT sequence, despite the absence of the 5'-ending C, is also capable of forming a 2Q-like higher order quadruplex by using a slightly different dimerization interface, as characterized by NMR spectroscopy. To the best of our knowledge, this is the first characterization of a quadruplex multimer formed by an oligodeoxynucleotide presenting a thymine at its 5'-end. Examples of such structures were observed previously only in crystals and in the presence of non-physiological cations. Our results expand the repertoire of DNA quadruplex nanostructures of chosen length and add further complexity to the structural polymorphism of G-rich DNA sequences.
在之前的工作中，我们已经证明，当在铵根或钾离子存在的情况下退火时，CGGTGGT 序列可以折叠成一种更高阶的 G-四链体结构（2Q），这种结构是由两个不寻常的 5'-5' 堆叠的 G(:C):G(:C):G(:C):G(:C) 平面八聚体形成的，这两个八聚体属于两个相同的四链平行 G-四链体。在本文中，我们讨论了标题核苷酸碱基 X 和 Y（其中 X 和 Y 代表 A、C、G 或 T）在 XGGYGGT 寡脱氧核苷酸形成的 2Q 结构的形成和稳定性中所起的作用。我们发现，上述二聚化途径不仅是 CGGTGGT 序列所特有的，而且对于所有剩余的 CGGYGGT 序列（Y = A、C 或 G）也是可能的。此外，我们发现，尽管 TGGAGGT 序列没有 5'-端的 C，但它也能够通过使用稍微不同的二聚化界面形成类似于 2Q 的高阶四链体，这一点通过 NMR 光谱学得到了表征。据我们所知，这是第一个由具有 5'-端胸腺嘧啶的寡脱氧核苷酸形成的四链体多聚体的特征描述，以前仅在晶体中和存在非生理阳离子的情况下观察到这种结构的例子。我们的结果扩展了所选长度的 DNA 四链体纳米结构的范围，并为富含 G 的 DNA 序列的结构多态性增加了进一步的复杂性。
