Department of Biosystems, Biosensors Group, KU Leuven-University of Leuven, 3001 Leuven, Belgium.
Department of Biosystems, Postharvest Group, KU Leuven-University of Leuven, 3001 Leuven, Belgium.
Int J Mol Sci. 2023 Sep 5;24(18):13686. doi: 10.3390/ijms241813686.
DNA-based enzymes, or DNAzymes, are single-stranded DNA sequences with the ability to catalyze various chemical reactions, including the cleavage of the bond between two RNA nucleotides. Lately, an increasing interest has been observed in these RNA-cleaving DNAzymes in the biosensing and therapeutic fields for signal generation and the modulation of gene expression, respectively. Additionally, multiple efforts have been made to study the effects of the reaction environment and the sequence of the catalytic core on the conversion of the substrate into product. However, most of these studies have only reported alterations of the general reaction course, but only a few have focused on how each individual reaction step is affected. In this work, we present for the first time a mathematical model that describes and predicts the reaction of the 10-23 RNA-cleaving DNAzyme. Furthermore, the model has been employed to study the effect of temperature, magnesium cations and shorter substrate-binding arms of the DNAzyme on the different kinetic rate constants, broadening the range of conditions in which the model can be exploited. In conclusion, this work depicts the prospects of such mathematical models to study and anticipate the course of a reaction given a particular environment.
基于 DNA 的酶,或 DNA 酶,是具有催化各种化学反应能力的单链 DNA 序列,包括切割两个 RNA 核苷酸之间的键。最近,人们对这些 RNA 切割 DNA 酶在生物传感和治疗领域的兴趣日益增加,分别用于信号产生和基因表达的调节。此外,已经做出了多种努力来研究反应环境和催化核心序列对底物转化为产物的影响。然而,这些研究大多只报告了一般反应过程的改变,但只有少数研究集中在如何影响每个单独的反应步骤。在这项工作中,我们首次提出了一个数学模型,该模型描述和预测了 10-23 RNA 切割 DNA 酶的反应。此外,该模型已被用于研究温度、镁阳离子和 DNA 酶较短的底物结合臂对不同动力学速率常数的影响,拓宽了模型可以利用的条件范围。总之,这项工作描述了这种数学模型在给定特定环境下研究和预测反应过程的前景。