Nielsen Jakob T, Arar Khalil, Petersen Michael
Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
Nucleic Acids Res. 2006 Apr 13;34(7):2006-14. doi: 10.1093/nar/gkl144. Print 2006.
We have determined the NMR solution structures of the quadruplexes formed by d(TGLGLT) and d(TL4T), where L denotes LNA (locked nucleic acid) modified G-residues. Both structures are tetrameric, parallel and right-handed and the native global fold of the corresponding DNA quadruplex is retained upon introduction of the LNA nucleotides. However, local structural alterations are observed owing to the locked LNA sugars. In particular, a distinct change in the sugar-phosphate backbone is observed at the G2pL3 and L2pL3 base steps and sequence dependent changes in the twist between tetrads are also seen. Both the LNA modified quadruplexes have raised thermostability as compared to the DNA quadruplex. The quadruplex-forming capability of d(TGLGLT) is of particular interest as it expands the design flexibility for stable parallel LNA quadruplexes and shows that LNA nucleotides can be mixed with DNA or other modified nucleic acids. As such, LNA-based quadruplexes can be decorated by a variety of chemical modifications. Such LNA quadruplex scaffolds might find applications in the developing field of nanobiotechnology.
我们已经确定了由d(TGLGLT)和d(TL4T)形成的四链体的核磁共振溶液结构，其中L表示锁核酸（LNA）修饰的G残基。这两种结构均为四聚体，平行且右手螺旋，并且在引入LNA核苷酸后保留了相应DNA四链体的天然整体折叠。然而，由于LNA糖的锁定作用，观察到了局部结构改变。特别是，在G2pL3和L2pL3碱基步处观察到糖磷酸骨架有明显变化，并且在四联体之间的扭曲中也看到了序列依赖性变化。与DNA四链体相比，两种LNA修饰的四链体都具有更高的热稳定性。d(TGLGLT)的四链体形成能力特别令人感兴趣，因为它扩展了稳定平行LNA四链体的设计灵活性，并表明LNA核苷酸可以与DNA或其他修饰的核酸混合。因此，基于LNA的四链体可以通过多种化学修饰进行修饰。这种基于LNA的四链体支架可能在纳米生物技术的发展领域中找到应用。
