Interplay of Structure, Hydration and Thermal Stability in Formacetal Modified Oligonucleotides: RNA May Tolerate Nonionic Modifications Better than DNA
Interplay of Structure, Hydration and Thermal Stability in Formacetal Modified Oligonucleotides: RNA May Tolerate Nonionic Modifications Better than DNA
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DOI：
10.1021/ja904926e
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发表时间：
2009-10-21
影响因子：
15
通讯作者：
Rozners, Eriks
中科院分区：
文献类型：
--
作者：
Kolarovic, Andrej;Schweizer, Emma;Rozners, Eriks
制备了尿苷和腺苷之间具有缩醛核苷键的DNA和RNA寡核苷酸，并用紫外热熔融法、渗透压法和X射线结晶学对其进行了研究。甲缩醛修饰对双螺旋RNA和DNA有显著不同的影响-甲缩醛每次修饰使RNA螺旋稳定+07摄氏度，但使DNA螺旋不稳定-1.6摄氏度。表面上疏水的甲缩醛对RNA的水合几乎没有影响，但减少了DNA的水合，这表明至少部分热稳定性的差异可能与水合的差异有关。修饰后的DNA的晶体结构表明，两个孤立的甲缩醛键几乎完美地吻合在一起的A型螺旋(十聚体)上，这表明RNA可能比DNA更能耐受非离子骨架的修饰。总体而言，甲缩醛似乎是一种很好的模拟rna中的磷酸键的方法，并且在基础研究和基于rna的基因控制策略(如rna干扰)中具有潜在的应用前景。
DNA and RNA oligonucleotides having formacetal internucleoside linkages between uridine and adenosine nucleosides have been prepared and studied using UV thermal melting, osmotic stress, and X-ray crystallography. Formacetal modifications have remarkably different effects on double helical RNA and DNA-the formacetal stabilizes the RNA helix by +07 degrees C but destabilizes the DNA helix by -1.6 degrees C per modification. The apparently hydrophobic formacetal has little effect on hydration of RNA but decreases the hydration of DNA, which suggests that at least part of the difference in thermal stability may be related to differences in hydration A crystal structure of modified DNA shows that two isolated formacetal linkages fit almost perfectly in an A-type helix (decamer) Taken together, the data suggest that RNA may tolerate nonionic backbone modifications better than DNA. Overall, formacetal appears to be an excellent mimic of phosphate linkage in RNA and an interesting modification for potential applications in fundamental studies and RNA-based gene control strategies, such as RNA interference