Catalytic Activities of Multimeric G-Quadruplex DNAzymes
Catalytic Activities of Multimeric G-Quadruplex DNAzymes
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DOI：
10.3390/catal9070613
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发表时间：
2019-07-01
期刊：
影响因子：
3.9
通讯作者：
Olorunniji, Femi J.
中科院分区：
文献类型：
--
作者：
Adeoye, Raphael, I;Osalaye, Dunsin S.;Olorunniji, Femi J.
G-四链体DNA酶是具有与氯高铁血红素结合在非共价复合物中的重复G4四联体的短DNA适体。这些G4/Hemin结构显示出多功能的过氧化物酶样催化活性，在生物传感和生物技术中具有广泛的潜在应用。目前的努力旨在更好地了解DNA酶催化的分子机制，以及设计提高其催化效率的策略。将G-四链体的离散单元多聚化以形成多价DNA酶是旨在增强DNA酶的过氧化物酶活性的新兴设计策略。虽然这种方法有希望产生更有活性的多价G-四链体DNA酶，但研究的例子很少，而且不清楚是什么因素决定了多聚体DNA酶催化活性的增强。在这项研究中，我们报告了五个G-四链体序列（AS 1411，Bcl-2，c-MYC，PS5.M和PS2.M）的多聚体的设计和表征。我们的研究结果表明，形成平行结构（AS 1411，Bcl-2，c-MYC）的G-四链体的多聚化导致单体单元之间的合作和/或协同相互作用的特征显着的速率增强。相反，形成非平行结构的DNA序列的多聚化（PS5.M和PS2.M）没有表现出类似水平的活性协同增加。这些结果表明，多价G4/氯化血红素结构的设计可能会导致一组新的通用和有效的DNA酶与增强的能力，催化过氧化物酶模拟反应。
G-quadruplex DNAzymes are short DNA aptamers with repeating G4 quartets bound in a non-covalent complex with hemin. These G4/Hemin structures exhibit versatile peroxidase-like catalytic activity with a wide range of potential applications in biosensing and biotechnology. Current efforts are aimed at gaining a better understanding of the molecular mechanism of DNAzyme catalysis as well as devising strategies for improving their catalytic efficiency. Multimerisation of discrete units of G-quadruplexes to form multivalent DNAzyes is an emerging design strategy aimed at enhancing the peroxidase activities of DNAzymes. While this approach holds promise of generating more active multivalent G-quadruplex DNAzymes, few examples have been studied and it is not clear what factors determine the enhancement of catalytic activities of multimeric DNAzymes. In this study, we report the design and characterisation of multimers of five G-quadruplex sequences (AS1411, Bcl-2, c-MYC, PS5.M and PS2.M). Our results show that multimerisation of G-quadruplexes that form parallel structure (AS1411, Bcl-2, c-MYC) leads to significant rate enhancements characteristic of cooperative and/or synergistic interactions between the monomeric units. In contrast, multimerisation of DNA sequences that form non-parallel structures (PS5.M and PS2.M) did not exhibit similar levels of synergistic increase in activities. These results show that design of multivalent G4/Hemin structures could lead to a new set of versatile and efficient DNAzymes with enhanced capacity to catalyse peroxidase-mimic reactions.