Inosine is an important RNA modification, furthermore RNA oxidation has gained interest due, in part, to its potential role in the development/progression of disease as well as on its impact on RNA structure and function. In this report we established the base pairing abilities of purine nucleobases G, I, A, as well as their corresponding, 8‐oxo‐7,8‐dihydropurine (common products of oxidation at the C8‐position of purines), and 8‐bromopurine (as probes to explore conformational changes), derivatives, namely 8‐oxoG, 8‐oxoI, 8‐oxoA, 8‐BrG, and 8‐BrI. Dodecamers of RNA were obtained using standard phosphoramidite chemistry via solid‐phase synthesis, and used as models to establish the impact that each of these nucleobases have on the thermal stability of duplexes, when base pairing to canonical and noncanonical nucleobases. Thermal stabilities were obtained from thermal denaturation transition (Tm) measurements, via circular dichroism (CD). The results were then rationalized using models of base pairs between two monomers, via density functional theory (DFT), that allowed us to better understand potential contributions from H‐bonding patterns arising from distinct conformations. Overall, some of the important results indicate that: (a) an anti‐I:syn‐A base pair provides thermal stability, due to the absence of the exocyclic amine; (b) 8‐oxoG base pairs like U, and does not induce destabilization within the duplex when compared to the pyrimidine ring; (c) a U:G wobble‐pair is only stabilized by G; and (d) 8‐oxoA displays an inherited base pairing promiscuity in this sequence context. Gaining a better understanding of how this oxidatively generated lesions potentially base pair with other nucleobases will be useful to predict various biological outcomes, as well as in the design of biomaterials and/or nucleotide derivatives with biological potential.

中文翻译：

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RNA A 型双链体中肌苷、鸟苷、腺苷及其相应的 8-氧代-7,8-二氢嘌呤和 8-溴嘌呤类似物的碱基配对能力的实验和理论合理化

肌苷是一种重要的 RNA 修饰，此外，RNA 氧化也引起了人们的兴趣，部分原因是其在疾病发生/进展中的潜在作用以及对 RNA 结构和功能的影响。在本报告中，我们建立了嘌呤核碱基 G、I、A 及其相应的 8-氧代-7,8-二氢嘌呤（嘌呤 C8 位氧化的常见产物）和 8- 的碱基配对能力。溴嘌呤（作为探索构象变化的探针）、衍生物，即 8-oxoG、8-oxoI、8-oxoA、8-BrG 和 8-BrI。RNA 的十二聚体是使用标准亚磷酰胺化学通过固相合成获得的，并用作模型来确定当与规范和非规范核碱基进行碱基配对时，每个核碱基对双链体热稳定性的影响。热稳定性通过圆二色性 (CD) 测量热变性转变 (Tm) 获得。然后通过密度泛函理论 (DFT) 使用两个单体之间的碱基对模型对结果进行合理化，这使我们能够更好地理解不同构象产生的氢键模式的潜在贡献。总的来说，一些重要的结果表明：（a）由于不存在环外胺，抗 I:syn-A 碱基对提供了热稳定性；(b) 8-oxoG 碱基对如 U，与嘧啶环相比不会引起双链体内的不稳定；(c) U:G 摆动对仅由 G 稳定；(d) 8-oxoA 在该序列背景下表现出遗传性碱基配对混乱。更好地了解这种氧化产生的损伤如何与其他核碱基潜在碱基对将有助于预测各种生物学结果，以及设计具有生物潜力的生物材料和/或核苷酸衍生物。