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有机汞寡核苷酸缀合物作为人工核糖核酸酶。

Organomercury oligonucleotide conjugates as artificial ribonucleases.

机构信息

Department of Chemistry, University of Turku, Henrikinkatu 2, 20500 Turku, Finland.

Department of Chemistry, University of Turku, Henrikinkatu 2, 20500 Turku, Finland.

出版信息

J Inorg Biochem. 2023 Oct;247:112331. doi: 10.1016/j.jinorgbio.2023.112331. Epub 2023 Jul 17.

DOI:10.1016/j.jinorgbio.2023.112331
PMID:37480764
Abstract

Two oligonucleotide conjugates sharing the same sequence but incorporating a different 5'-terminal organometallic moiety were synthesized, by either direct mercuration in solution or oximation with an organomercury aldehyde on solid support. The potential of these conjugates to serve as new type of artificial ribonucleases was tested with a complementary 2´-O-methyl-RNA target sequence featuring a single cleavable RNA phosphodiester linkage. Both organomercury oligonucleotides greatly outperformed their metal-free counterparts as well as the previously reported small molecule organomercury RNA cleaving agent in catalytic activity, providing an important proof-of-concept. Compared to state-of-the-art metal-dependent artificial ribonucleases, however, the observed activity was modest.

摘要

两种寡核苷酸缀合物具有相同的序列,但在 5'-末端含有不同的有机金属部分,它们通过溶液中的直接汞化或在固体支持物上与有机汞醛肟化反应合成。这些缀合物作为新型人工核糖核酸酶的潜力通过具有单个可切割 RNA 磷酸二酯键的互补 2´-O-甲基-RNA 靶序列进行了测试。两种有机汞寡核苷酸在催化活性方面都远远优于其无金属对应物以及之前报道的小分子有机汞 RNA 切割剂,这提供了一个重要的概念验证。然而,与最先进的金属依赖性人工核糖核酸酶相比,观察到的活性适中。

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1
Organomercury oligonucleotide conjugates as artificial ribonucleases.有机汞寡核苷酸缀合物作为人工核糖核酸酶。
J Inorg Biochem. 2023 Oct;247:112331. doi: 10.1016/j.jinorgbio.2023.112331. Epub 2023 Jul 17.
2
Di(azacrown) conjugates of 2'-O-methyl oligoribonucleotides as sequence-selective artificial ribonucleases.2'-O-甲基寡核糖核苷酸的二(氮杂冠醚)缀合物作为序列选择性人工核糖核酸酶。
Bioconjug Chem. 2007 Sep-Oct;18(5):1583-92. doi: 10.1021/bc070071o. Epub 2007 Aug 21.
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Sequence-specific artificial ribonucleases. I. Bis-imidazole-containing oligonucleotide conjugates prepared using precursor-based strategy.序列特异性人工核糖核酸酶。I. 使用基于前体的策略制备的含双咪唑的寡核苷酸缀合物。
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Site-Selective Artificial Ribonucleases: Renaissance of Oligonucleotide Conjugates for Irreversible Cleavage of RNA Sequences.位点选择性人工核糖核酸酶:用于RNA序列不可逆切割的寡核苷酸缀合物的复兴
Molecules. 2021 Mar 19;26(6):1732. doi: 10.3390/molecules26061732.
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Artificial ribonucleases: oligonucleotide-peptide conjugates that cleave RNA at the GpX and PypA phosphodiester bonds.人工核糖核酸酶:在GpX和PypA磷酸二酯键处切割RNA的寡核苷酸-肽缀合物。
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Making oligonucleotide conjugates and breaking oligonucleotides.制备寡核苷酸缀合物并切割寡核苷酸。
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Creating RNA bulges: cleavage of RNA in RNA/DNA duplexes by metal ion catalysis.形成RNA凸起:通过金属离子催化切割RNA/DNA双链体中的RNA。
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Artificial ribonucleases.人工核糖核酸酶
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