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锌指 DNA 酶:从溶液化学到分析、材料和治疗应用。

Zn -Dependent DNAzymes: From Solution Chemistry to Analytical, Materials and Therapeutic Applications.

机构信息

Department of Chemistry, Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, Ontario, N2L 3G1, Canada.

Department of Food and Biological Science, College of Agricultural, Yanbian University, Yanbian Chaoxianzuzizhizhou, Yanji, 133002, P. R. China.

出版信息

Chembiochem. 2021 Mar 2;22(5):779-789. doi: 10.1002/cbic.202000586. Epub 2020 Nov 11.

DOI:10.1002/cbic.202000586
PMID:33007113
Abstract

Since 1994, deoxyribozymes or DNAzymes have been in vitro selected to catalyze various types of reactions. Metal ions play a critical role in DNAzyme catalysis, and Zn is a very important one among them. Zn has good biocompatibility and can be used for intracellular applications. Chemically, Zn is a Lewis acid and it can bind to both the phosphate backbone and the nucleobases of DNA. Zn undergoes hydrolysis even at neutral pH, and the partially hydrolyzed polynuclear complexes can affect the interactions with DNA. These features have made Zn a unique cofactor for DNAzyme reactions. This review summarizes Zn -dependent DNAzymes with an emphasis on RNA-/DNA-cleaving reactions. A key feature is the sharp Zn concentration and pH-dependent activity for many of the DNAzymes. The applications of these DNAzymes as biosensors for Zn , as therapeutic agents to cleave intracellular RNA, and as chemical biology tools to manipulate DNA are discussed. Future studies can focus on the selection of new DNAzymes with improved performance and detailed biochemical characterizations to understand the role of Zn , which can facilitate practical applications of Zn -dependent DNAzymes.

摘要

自 1994 年以来,脱氧核酶或 DNA 酶已在体外被筛选出来以催化各种类型的反应。金属离子在 DNA 酶催化中起着关键作用,其中 Zn 是非常重要的一种。Zn 具有良好的生物相容性,可用于细胞内应用。在化学上,Zn 是一种路易斯酸,它可以与 DNA 的磷酸骨架和碱基结合。即使在中性 pH 下,Zn 也会发生水解,部分水解的多核配合物会影响与 DNA 的相互作用。这些特性使 Zn 成为 DNA 酶反应的独特辅助因子。本文综述了依赖 Zn 的 DNA 酶,重点介绍了 RNA-/DNA 切割反应。一个关键特征是许多 DNA 酶对 Zn 的浓度和 pH 依赖性活性都很高。讨论了这些 DNA 酶作为 Zn 生物传感器的应用、作为切割细胞内 RNA 的治疗剂,以及作为化学生物学工具来操纵 DNA 的应用。未来的研究可以集中在选择具有改进性能和详细生化特性的新型 DNA 酶上,以了解 Zn 的作用,从而促进依赖 Zn 的 DNA 酶的实际应用。

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