INSERM U869, European Institute of Chemistry and Biology, Bordeaux University, 2 rue Robert Escarpit, Pessac, France.
Biochimie. 2011 Mar;93(3):399-408. doi: 10.1016/j.biochi.2010.10.011. Epub 2010 Oct 27.
Tetramolecular G-quadruplexes result from the association of four guanine-rich strands. Modification of the backbone strand or the guanine bases of the oligonucleotide may improve stability or introduce new functionalities. In this regard, the 8 position of a guanosine is particularly suitable for introduction of modifications since as it is positioned in the groove of the quadruplex structure. Modifications at this position should not interfere with structural assembly as would changes at Watson-Crick and Hoogsteen sites. In this study, we investigated the effect of an 8-methyl-2'-deoxyguanosine residue (M) on the structure and stability of tetramolecular parallel G-quadruplexes. In some cases, the presence of this residue resulted in the formation of unusual quadruplex structures containing all-syn tetrads. Furthermore, the modified nucleoside M at the 5'-end of the sequence accelerated quadruplex formation by 15-fold or more relative to the unmodified oligonucleotide, which makes this nucleobase an attractive replacement for guanine in the context of tetramolecular parallel quadruplexes.
四聚体 G-四链体是由四个富含鸟嘌呤的链段缔合而成。寡核苷酸的骨架链或鸟嘌呤碱基的修饰可以提高稳定性或引入新的功能。在这方面，鸟苷的 8 位特别适合引入修饰，因为它位于四链体结构的沟槽中。与 Watson-Crick 和 Hoogsteen 位点的变化不同，该位置的修饰不应干扰结构组装。在这项研究中，我们研究了 8-甲基-2'-脱氧鸟苷残基 (M) 对四聚体平行 G-四链体结构和稳定性的影响。在某些情况下，该残基的存在导致形成了含有全顺四联体的异常四链体结构。此外，与未修饰的寡核苷酸相比，序列 5'-末端的修饰核苷 M 使四聚体形成速度加快了 15 倍或更多，这使得该碱基在四聚体平行四链体中成为鸟嘌呤的有吸引力的替代品。
