Sulfonylation of RNA 2'-OH groups.
Sulfonylation of RNA 2'-OH groups.
复制标题
RNA 2'-OH基团的磺酰基。
DOI：
10.1021/acscentsci.2c01237
复制
发表时间：
2023-03-22
影响因子：
18.2
通讯作者：
Kool, Eric T.
中科院分区：
文献类型：
--
作者：
Chatterjee, Sayantan;Shioi, Ryuta;Kool, Eric T.
RNA 2 ' -OH基团在水中的亲核反应性已被证明在探测、标记和结合RNA方面广泛有用。迄今为止，选择核糖2 ' -OH的反应仅限于与寿命短的羰基亲电试剂形成键。在这里，我们报道了许多活化的小分子磺酰基物质可以在水中表现出延长的寿命并保持2 ' -OH反应性。这些数据表明所选试剂具有良好的水溶性，并且在化学计量和超化学计量产率下成功地进行rna选择反应，特别是芳基磺酰基三唑类。我们报告说，后者在水环境中比大多数先前的碳亲电试剂稳定得多，并且耐受二氧化硅色谱。此外，开发了一种叠氮取代磺酰三唑试剂，通过点击化学将标签引入RNA。除了高产率的反应，我们发现RNA磺酰化也可以在提供结构绘图所需的痕量产率的条件下进行。与酰化一样，该反应对未配对的核苷酸比双链结构中的核苷酸有选择性，并且磺酸加合物会导致逆转录酶停止，这表明在RNA结构分析中有潜在的用途。在人类细胞中证实了rRNA的探测，表明可能的细胞渗透性。磺酰基试剂类使RNA应用的控制，选择性，多功能性和易于制备的新水平。我们介绍了磺酰基试剂作为一类新的RNA 2 ' -OH反应小分子。这些分子稳定，易于合成和纯化，可用于结构作图和共价标记。
The nucleophilic reactivity of RNA 2′-OH groups in water has proven broadly useful in probing, labeling, and conjugating RNA. To date, reactions selective to ribose 2′-OH have been limited to bond formation with short-lived carbonyl electrophiles. Here we report that many activated small-molecule sulfonyl species can exhibit extended lifetimes in water and retain 2′-OH reactivity. The data establish favorable aqueous solubility for selected reagents and successful RNA-selective reactions at stoichiometric and superstoichiometric yields, particularly for aryl sulfonyltriazole species. We report that the latter are considerably more stable than most prior carbon electrophiles in aqueous environments and tolerate silica chromatography. Furthermore, an azide-substituted sulfonyltriazole reagent is developed to introduce labels into RNA via click chemistry. In addition to high-yield reactions, we find that RNA sulfonylation can also be performed under conditions that give trace yields necessary for structure mapping. Like acylation, the reaction occurs with selectivity for unpaired nucleotides over those in the duplex structure, and a sulfonate adduct causes reverse transcriptase stops, suggesting potential use in RNA structure analysis. Probing of rRNA is demonstrated in human cells, indicating possible cell permeability. The sulfonyl reagent class enables a new level of control, selectivity, versatility, and ease of preparation for RNA applications. We introduce sulfonyl reagents as a new class of RNA 2′-OH reactive small molecules. These molecules are stable, easy to synthesize and purify, and useful for structure mapping and covalent labeling.
登录
查看更多内容
影响因子：
7.3
作者：
Ciganda, Martin;Williams, Noreen
通讯作者：
Williams, Noreen
影响因子：
15
作者：
Gushwa, Nathan N.;Kang, Sumin;Chen, Jing;Taunton, Jack
通讯作者：
Taunton, Jack
影响因子：
15
作者：
Alexander, Seth C.;Busby, Kayla N.;Devaraj, Neal K.
通讯作者：
Devaraj, Neal K.
DOI：
10.1073/pnas.0806929106
发表时间：
2009-01-06
影响因子：
11.1
作者：
Deigan, Katherine E.;Li, Tian W.;Weeks, Kevin M.
通讯作者：
Weeks, Kevin M.
影响因子：
14.8
作者：
Hahm, Heung Sik;Toroitich, Emmanuel K.;Hsu, Ku-Lung
通讯作者：
Hsu, Ku-Lung