Repurposing Antiviral Drugs for Orthogonal RNA-Catalyzed Labeling of RNA.,Angewandte Chemie International Edition

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Repurposing Antiviral Drugs for Orthogonal RNA-Catalyzed Labeling of RNA.
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2020-03-11 , DOI: 10.1002/anie.202001300
Mohammad Ghaem Maghami _{1,

2} , Surjendu Dey ₁ , Ann-Kathrin Lenz ₁ , Claudia Höbartner _{1,

2}

Affiliation

In vitro selected ribozymes are promising tools for site‐specific labeling of RNA. Previously known nucleic acid catalysts attached fluorescently labeled adenosine or guanosine derivatives through 2′,5′‐branched phosphodiester bonds to the RNA of interest. Herein, we report new ribozymes that use orthogonal substrates, derived from the antiviral drug tenofovir, and attach bioorthogonal functional groups, as well as affinity handles and fluorescent reporter units through a hydrolytically more stable phosphonate ester linkage. The tenofovir transferase ribozymes were identified by in vitro selection and are orthogonal to nucleotide transferase ribozymes. As genetically encodable functional RNAs, these ribozymes may be developed for potential cellular applications. The orthogonal ribozymes addressed desired target sites in large RNAs in vitro, as shown by fluorescent labeling of E. coli 16S and 23S rRNAs in total cellular RNA.

中文翻译：

重新利用抗病毒药物用于 RNA 的正交 RNA 催化标记。

体外选择的核酶是 RNA 位点特异性标记的有前途的工具。先前已知的核酸催化剂通过 2',5'-分支的磷酸二酯键将荧光标记的腺苷或鸟苷衍生物连接到目标 RNA。在此，我们报告了使用正交底物的新核酶，该核酶源自抗病毒药物替诺福韦，并通过水解更稳定的膦酸酯键连接生物正交官能团，以及亲和手柄和荧光报告单元。替诺福韦转移酶核酶通过体外选择鉴定并且与核苷酸转移酶核酶正交。作为可遗传编码的功能性 RNA，这些核酶可以开发用于潜在的细胞应用。正交核酶在体外处理大 RNA 中所需的靶位点，细胞总 RNA 中的大肠杆菌16S 和 23S rRNA。

更新日期：2020-03-11

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