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芳基汞配合物对 RNA 模型化合物的断裂作用。

Cleavage of an RNA Model Compound by an Arylmercury Complex.

机构信息

Department of Chemistry, University of Turku, Vatselankatu 2, 20014, Turku, Finland.

出版信息

Chembiochem. 2021 May 14;22(10):1761-1764. doi: 10.1002/cbic.202000799. Epub 2021 Feb 24.

DOI:10.1002/cbic.202000799
PMID:33448598
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8247959/
Abstract

A water-soluble arylmercury complex has been synthesized, and its ability to catalyze the cleavage of the phosphodiester linkage of the RNA model compound adenylyl-3',5'-(2',3'-O-methyleneadenosine) has been assessed over a pH range of 3-8.5 and a catalyst concentration range of 0-7 mM. In the presence of 1 mM catalyst, the observed pH-rate profile featured a new pH-independent region between pH 6 and 7, the catalyzed reaction being as much as eight times faster than the background reaction. At pH 7, the acceleration increased linearly from three- to 17-fold upon increasing the catalyst concentration from 1 to 7 mM. The linear dependence indicates a relatively low affinity of the catalyst for the substrate and, hence, the potential for considerable improvement on tethering to an appropriate targeting group, such as an oligonucleotide.

摘要

已合成了一种水溶性芳基汞配合物,并在 pH 值为 3-8.5 和催化剂浓度为 0-7mM 的范围内评估了其催化 RNA 模型化合物腺苷酰基-3',5'-(2',3'-O-亚甲基腺苷)的磷酸二酯键断裂的能力。在 1mM 催化剂存在下,观察到的 pH-速率曲线在 pH 6 和 7 之间呈现出新的 pH 独立区域,催化反应比背景反应快多达 8 倍。在 pH 7 时,随着催化剂浓度从 1mM 增加到 7mM,加速作用从 3 倍线性增加到 17 倍。线性依赖性表明催化剂与底物的亲和力相对较低,因此,通过将其连接到适当的靶向基团(例如寡核苷酸),仍有很大的改进空间。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10d6/8247959/cf0735cca2da/CBIC-22-1761-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10d6/8247959/cc86529c3c62/CBIC-22-1761-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10d6/8247959/1f472254a050/CBIC-22-1761-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10d6/8247959/ec9c892a8f68/CBIC-22-1761-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10d6/8247959/37b7b8f368d3/CBIC-22-1761-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10d6/8247959/cf0735cca2da/CBIC-22-1761-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10d6/8247959/cc86529c3c62/CBIC-22-1761-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10d6/8247959/1f472254a050/CBIC-22-1761-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10d6/8247959/ec9c892a8f68/CBIC-22-1761-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10d6/8247959/37b7b8f368d3/CBIC-22-1761-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10d6/8247959/cf0735cca2da/CBIC-22-1761-g004.jpg

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本文引用的文献

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PEGylation and Cell-Penetrating Peptides: Glimpse into the Past and Prospects in the Future.聚乙二醇化和细胞穿透肽:过去的一瞥和未来的展望。
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The Zn(II)-1,4,7-Trimethyl-1,4,7-Triazacyclononane Complex: A Monometallic Catalyst Active in Two Protonation States.锌(II)-1,4,7-三甲基-1,4,7-三氮杂环壬烷配合物:一种在两种质子化状态下都具有活性的单金属催化剂。
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Phosphodiester models for cleavage of nucleic acids.
核酸切割的磷酸二酯模型。
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Zinc Ion-Dependent Peptide Nucleic Acid-Based Artificial Enzyme that Cleaves RNA-Bulge Size and Sequence Dependence.基于锌离子依赖的肽核酸的人工酶,可切割 RNA 突环大小和序列依赖性。
Molecules. 2017 Oct 29;22(11):1856. doi: 10.3390/molecules22111856.
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Characterization of Highly Efficient RNA-Cleaving DNAzymes that Function at Acidic pH with No Divalent Metal-Ion Cofactors.在无二价金属离子辅因子条件下于酸性pH值发挥作用的高效RNA切割脱氧核酶的特性分析
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Polyethylene glycol (PEG): a versatile polymer for pharmaceutical applications.聚乙二醇(PEG):一种用于药物应用的多功能聚合物。
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PEGylation as a strategy for improving nanoparticle-based drug and gene delivery.聚乙二醇化作为一种改善基于纳米颗粒的药物和基因递送的策略。
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Sequence-specific RNA cleavage by PNA conjugates of the metal-free artificial ribonuclease tris(2-aminobenzimidazole).无金属人工核糖核酸酶三(2-氨基苯并咪唑)的肽核酸缀合物对序列特异性RNA的切割作用
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