Dipartimento di Chimica delle Sostanze Naturali, Università degli Studi di Napoli Federico II, Via D. Montesano 49, I-80131 Napoli, Italy.
Nucleic Acids Res. 2012 Jan;40(1):461-75. doi: 10.1093/nar/gkr670. Epub 2011 Sep 9.
In this article, we report a structural study, based on NMR and CD spectroscopies, and molecular modelling of all possible d(TG(3)T) and d(TG(4)T) analogues containing two 8-methyl-2'-deoxyguanosine residues (M). Particularly, the potential ability of these modified residues to orientate the strands and then to affect the folding topology of tetramolecular quadruplex structures has been investigated. Oligodeoxynucleotides (ODNs) TMMGT (T12) and TMMGGT (F12) form parallel tetramolecular quadruplexes, characterized by an all-syn M-tetrad at the 5'-side stacked to all-anti M- and G-tetrads. ODNs TMGMT (T13) and TMGGMT (F14) form parallel tetramolecular quadruplexes, in which an all-anti G core is sandwiched between two all-syn M-tetrads at the 5'- and the 3'-side. Notably, the quadruplex formed by T13 corresponds to an unprecedented structure in which the syn residues exceed in number the anti ones. Conversely, ODN TGMGMT (F24) adopts a parallel arrangement in which all-anti G-tetrads alternate with all-syn M-tetrads. Most importantly, all data strongly suggest that ODN TMGMGT (F13) forms an unprecedented anti-parallel tetramolecular quadruplex in which G and M residues adopt anti and syn glycosidic conformations, respectively. This article opens up new understandings and perspectives about the intricate relationship between the quadruplex strands orientation and the glycosidic conformation of the residues.
在本文中，我们报道了一项基于 NMR 和 CD 光谱学以及分子建模的研究，研究了所有可能包含两个 8-甲基-2'-脱氧鸟苷残基（M）的 d(TG(3)T)和 d(TG(4)T)类似物的结构。特别是，研究了这些修饰残基定向链的潜在能力，以及它们如何影响四链体构象的折叠拓扑结构。寡脱氧核苷酸（ODN）TMMGT（T12）和 TMMGGT（F12）形成平行四链体构象，其特征是在 5'-侧堆积的全顺式 M-四联体与全反式 M-和 G-四联体相连。ODN TMGMT（T13）和 TMGGMT（F14）形成平行四链体构象，其中全反式 G 核夹在两个全顺式 M-四联体之间，位于 5'-和 3'-侧。值得注意的是，T13 形成的四链体是一种前所未有的结构，其中顺式残基的数量超过反式残基。相反，ODN TGMGMT（F24）采用平行排列，其中全反式 G-四联体与全顺式 M-四联体交替排列。最重要的是，所有数据都强烈表明，ODN TMGMGT（F13）形成了一种前所未有的反平行四链体构象，其中 G 和 M 残基分别采用反式和顺式糖苷构象。本文为理解四链体构象的方向性与残基糖苷构象之间的复杂关系提供了新的认识和视角。
