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用 2-氨基咪唑激活的核苷酸增强非酶 RNA 复制。

Enhanced Nonenzymatic RNA Copying with 2-Aminoimidazole Activated Nucleotides.

机构信息

Howard Hughes Medical Institute, Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital , Boston, Massachusetts 02114, United States.

出版信息

J Am Chem Soc. 2017 Feb 8;139(5):1810-1813. doi: 10.1021/jacs.6b13148. Epub 2017 Jan 24.

DOI:10.1021/jacs.6b13148
PMID:28117989
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6326525/
Abstract

Achieving efficient nonenzymatic replication of RNA is an important step toward the synthesis of self-replicating protocells that may mimic early forms of life. Despite recent progress, the nonenzymatic copying of templates containing mixed sequences remains slow and inefficient. Here we demonstrate that activating nucleotides with 2-aminoimidazole results in superior reaction kinetics and improved yields of primer extension reaction products. This new leaving group significantly accelerates monomer addition as well as trimer-assisted RNA primer extension, allowing efficient copying of a variety of short RNA templates with mixed sequences.

摘要

实现 RNA 的高效非酶复制是合成可能模拟早期生命形式的自我复制原细胞的重要步骤。尽管最近取得了进展,但包含混合序列的模板的非酶复制仍然缓慢且效率低下。在这里,我们证明用 2-氨基咪唑激活核苷酸会导致反应动力学更好,并提高引物延伸反应产物的产率。这种新的离去基团显著加速单体的添加以及三聚体辅助的 RNA 引物延伸,从而能够有效地复制各种具有混合序列的短 RNA 模板。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8a3/6326525/fd9c31d6e520/ja-2016-13148b_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8a3/6326525/fd1156d0b7ae/ja-2016-13148b_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8a3/6326525/c99395e29aaf/ja-2016-13148b_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8a3/6326525/54538720fbf9/ja-2016-13148b_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8a3/6326525/fd9c31d6e520/ja-2016-13148b_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8a3/6326525/fd1156d0b7ae/ja-2016-13148b_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8a3/6326525/c99395e29aaf/ja-2016-13148b_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8a3/6326525/54538720fbf9/ja-2016-13148b_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8a3/6326525/fd9c31d6e520/ja-2016-13148b_0004.jpg

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Nat Chem. 2017 Apr;9(4):303-309. doi: 10.1038/nchem.2664. Epub 2016 Nov 21.
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A Highly Reactive Imidazolium-Bridged Dinucleotide Intermediate in Nonenzymatic RNA Primer Extension.非酶促 RNA 引物延伸中具有高反应性的咪唑桥联二核苷酸中间体。
J Am Chem Soc. 2016 Sep 14;138(36):11996-2002. doi: 10.1021/jacs.6b07977. Epub 2016 Sep 1.
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Nonenzymatic copying of RNA templates containing all four letters is catalyzed by activated oligonucleotides.
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