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通过简单化学修饰将人工金属核酸酶靶向至DNA及其对催化作用的显著影响。

Targeting an Artificial Metal Nuclease to DNA by a Simple Chemical Modification and Its Drastic Effect on Catalysis.

作者信息

Castilho Nathalia, Gabriel Philipe, Camargo Tiago Pacheco, Neves Ademir, Terenzi Hernán

机构信息

Centro de Biologia Molecular Estrutural, Departamento de Bioquímica, Universidade Federal de Santa Catarina, 88040900 Florianópolis-SC, Brazil.

Departamento de Química, Universidade Federal de Santa Catarina, 88040900 Florianópolis-SC, Brazil.

出版信息

ACS Med Chem Lett. 2019 Aug 12;11(3):286-291. doi: 10.1021/acsmedchemlett.9b00289. eCollection 2020 Mar 12.

Abstract

A novel metal complex was synthesized containing a purine derived ligand in order to increase its binding to DNA. We observed a huge increase in nuclease activity and, quite interestingly, an improvement on DNA sequence selectivity. A potential site of specific cleavage in the presence of a reductant in the reaction medium is suggested. We were able to synthesize a novel metal nuclease with improved activity on DNA, and with sequence specificity when exposed to a coreactant, this opens up new possibilities to create site specific and redox status modulated artificial nucleases.

摘要

合成了一种含有嘌呤衍生配体的新型金属配合物,以增强其与DNA的结合。我们观察到核酸酶活性大幅增加,而且非常有趣的是,DNA序列选择性也有所提高。提出了在反应介质中存在还原剂时特定切割的潜在位点。我们能够合成一种对DNA具有更高活性且在暴露于共反应物时具有序列特异性的新型金属核酸酶,这为创建位点特异性和氧化还原状态调节的人工核酸酶开辟了新的可能性。

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