Electrophilic water-soluble compounds have proven versatile in reacting selectively with 2′-OH groups in RNA, enabling structure mapping, probing, caging, labeling, crosslinking, and conjugation of RNAs in vitro and in living cells. While early work focused on one or two types of reagents with limited properties, recent studies have greatly diversified the structure, properties, and applications of these reagents. Here we review the scope of documented RNA hydroxyl-reactive species reported to date, with an eye to the effects of chemical structure on reactivity with RNA and other useful properties. Multiple forms of carbonyl electrophiles are now known to react at the 2′-OH, and recently, sulfonyl and aryl electrophiles have also been documented to form bonds there in high yields as well. In addition to electrophilicity, data also point to significant effects of reagent stability, steric bulk, and chirality on reaction yields and selectivity. Finally, we outline reagent properties and principles that define utility in applications with RNA, with an eye to the design of future reagents.

中文翻译：

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修饰水中 RNA 2′-OH 的试剂的化学多样性：综述


事实证明，亲电水溶性化合物可与 RNA 中的 2′-OH 基团选择性反应，从而在体外和活细胞中实现 RNA 的结构绘图、探测、笼蔽、标记、交联和缀合。虽然早期的工作集中在一种或两种性质有限的试剂上，但最近的研究极大地多样化了这些试剂的结构、性质和应用。在这里，我们回顾了迄今为止报道的 RNA 羟基反应物质的范围，着眼于化学结构对 RNA 反应性和其他有用特性的影响。现在已知多种形式的羰基亲电子试剂在 2'-OH 处发生反应，最近，磺酰基和芳基亲电子试剂也被证明可以在那里以高产率形成键。除了亲电性之外，数据还表明试剂稳定性、空间体积和手性对反应产率和选择性的显着影响。最后，我们概述了定义 RNA 应用中实用性的试剂特性和原理，并着眼于未来试剂的设计。