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新型化学修饰 RNA 构建体的合成策略,以发夹和锤头核酶为例。

New strategy for the synthesis of chemically modified RNA constructs exemplified by hairpin and hammerhead ribozymes.

机构信息

School of Chemistry, University of Southampton, Highfield, Southampton, SO17 1BJ, United Kingdom.

出版信息

Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15329-34. doi: 10.1073/pnas.1006447107. Epub 2010 Aug 16.

DOI:10.1073/pnas.1006447107
PMID:20713730
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2932611/
Abstract

The CuAAC reaction (click chemistry) has been used in conjunction with solid-phase synthesis to produce catalytically active hairpin ribozymes around 100 nucleotides in length. Cross-strand ligation through neighboring nucleobases was successful in covalently linking presynthesized RNA strands with high efficiency (trans-ligation). In an alternative strategy, intrastrand click ligation was employed to produce a functional hammerhead ribozyme containing a novel nucleic acid backbone mimic at the catalytic site (cis-ligation). The ability to synthesize long RNA strands by a combination of solid-phase synthesis and click ligation is an important addition to RNA chemistry. It is compatible with a plethora of site-specific modifications and is applicable to the synthesis of many biologically important RNA molecules.

摘要

铜催化的叠氮-炔环加成反应(点击化学)已被用于与固相合成相结合,以生产大约 100 个核苷酸长的催化活性发夹核酶。通过相邻碱基的跨链连接,可以有效地将预合成的 RNA 链进行共价连接(反式连接)。在另一种策略中,采用链内点击连接来产生具有新颖核酸骨架模拟物的功能锤头核酶(顺式连接)。通过固相合成和点击连接相结合来合成长的 RNA 链的能力是 RNA 化学的一个重要补充。它与大量的位点特异性修饰兼容,并且适用于许多生物重要的 RNA 分子的合成。

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本文引用的文献

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Molecular assembly for high-performance bivalent nucleic acid inhibitor.用于高性能二价核酸抑制剂的分子组装
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