Department of Chemistry, McGill University, Montreal, QC H3A 2K6, Canada.
Nucleic Acids Res. 2010 Apr;38(7):2498-511. doi: 10.1093/nar/gkp1225. Epub 2010 Jan 13.
Hybrids of RNA with arabinonucleic acids 2'F-ANA and ANA have very similar structures but strikingly different thermal stabilities. We now present a thorough study combining NMR and other biophysical methods together with state-of-the-art theoretical calculations on a fully modified 10-mer hybrid duplex. Comparison between the solution structure of 2'F-ANARNA and ANARNA hybrids indicates that the increased binding affinity of 2'F-ANA is related to several subtle differences, most importantly a favorable pseudohydrogen bond (2'F-purine H8) which contrasts with unfavorable 2'-OH-nucleobase steric interactions in the case of ANA. While both 2'F-ANA and ANA strands maintained conformations in the southern/eastern sugar pucker range, the 2'F-ANA strand's structure was more compatible with the A-like structure of a hybrid duplex. No dramatic differences are found in terms of relative hydration for the two hybrids, but the ANARNA duplex showed lower uptake of counterions than its 2'F-ANARNA counterpart. Finally, while the two hybrid duplexes are of similar rigidities, 2'F-ANA single strands may be more suitably preorganized for duplex formation. Thus the dramatically increased stability of 2'F-ANARNA and ANARNA duplexes is caused by differences in at least four areas, of which structure and pseudohydrogen bonding are the most important.
具有阿拉伯糖核酸 2'F-ANA 和 ANA 的 RNA 杂种具有非常相似的结构，但热稳定性却截然不同。我们现在通过 NMR 和其他生物物理方法以及最先进的全修饰 10 聚体杂种双链体理论计算，对其进行了全面研究。2'F-ANARNA 和 ANARNA 杂种的溶液结构比较表明，结合亲和力的增加与几个细微的差异有关，最重要的是有利的假氢键（2'F-嘌呤 H8），这与 ANA 的不利 2'-OH-碱基位阻相互作用形成对比。虽然 2'F-ANA 和 ANA 链都保持在南部/东部糖环构象范围内，但 2'F-ANA 链的结构与杂种双链体的 A 样结构更相容。两种杂种的相对水合作用没有明显差异，但 ANARNA 双链体的抗衡离子摄取量低于其 2'F-ANARNA 对应物。最后，虽然两种杂种双链体的刚性相似，但 2'F-ANA 单链可能更适合双链体形成。因此，2'F-ANARNA 和 ANARNA 双链体稳定性的显著增加是由至少四个方面的差异引起的，其中结构和假氢键最重要。
