Keniry M A, Owen E A, Shafer R H
Research School of Chemistry, The Australian National University, Australia and Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA 94143-0446, USA.
Nucleic Acids Res. 1997 Nov 1;25(21):4389-92. doi: 10.1093/nar/25.21.4389.
The loop of four thymines in the sodium form of the dimeric folded quadruplex [d(G3T4G3)]2 assumes a well-defined structure in which hydrogen bonding between the thymine bases appears to contribute to the stability and final conformation of the quadruplex. We have investigated the importance of the loop interactions by systematically replacing each thymine in the loop with a cytosine. The quadruplexes formed by d(G3CT3G3), d(G3TCT2G3), d(G3T2CTG3) and d(G3T3CG3) in the presence of 150 mM Na+ were studied by gel mobility, circular dichroism and 1H NMR spectroscopy. The major species formed by d(G3CT3G3), d(G3TCT2G3) and d(G3T3CG3) at 1 mM strand concentration at neutral pH is a dimeric folded quadruplex. d(G3T2CTG3) has anomalous behaviour and associates into a greater percentage of linear four-stranded quadruplex than the other three oligonucleotides at neutral pH and at the same concentration. The linear four-stranded quadruplex has a greater tendency to oligomerize to larger ill-defined structures, as demonstrated by broad 1H NMR resonances. At pH 4, when the cytosine is protonated, there is a greater tendency for each of the oligonucleotides to form some four-stranded linear quadruplex, except for d(G3T2CTG3), which has the reverse tendency. The experimental results are discussed in terms of hydrogen bonding within the thymine loop.
二聚体折叠四重链体[d(G3T4G3)]2的钠盐形式中由四个胸腺嘧啶组成的环呈现出一种明确的结构，其中胸腺嘧啶碱基之间的氢键似乎有助于四重链体的稳定性和最终构象。我们通过系统地将环中的每个胸腺嘧啶替换为胞嘧啶，研究了环相互作用的重要性。利用凝胶迁移率、圆二色性和1H NMR光谱研究了在150 mM Na+存在下由d(G3CT3G3)、d(G3TCT2G3)、d(G3T2CTG3)和d(G3T3CG3)形成的四重链体。在中性pH值下，1 mM链浓度时，d(G3CT3G3)、d(G3TCT2G3)和d(G3T3CG3)形成的主要物种是二聚体折叠四重链体。d(G3T2CTG3)具有异常行为，在中性pH值和相同浓度下，与其他三种寡核苷酸相比，其形成线性四链四重链体的比例更高。如宽的1H NMR共振所示，线性四链四重链体更倾向于寡聚形成更大的不明确结构。在pH 4时，当胞嘧啶质子化时，除了具有相反倾向的d(G3T2CTG3)外，每种寡核苷酸形成一些四链线性四重链体的倾向更大。根据胸腺嘧啶环内的氢键对实验结果进行了讨论。
