8,5'-Cyclo 2'-deoxyadenosine对10-23DNA酶的活性的影响:实验和理论研究
Marcin Cieślak1, Bolesław T Karwowski1
1Food Science Department, Faculty of Pharmacy, Medical University of Lodz, ul. Muszynskiego 1, 90-151 Lodz, Poland.
International journal of molecular sciences
|March 13, 2024
概括
在催化循环中将DNAzymes 10-23 (Dz10-23) 与循环脱氧腺素 (cdA) 进行修改,降低了它们的RNA裂变活性. 这种抑制取决于cda.
科学领域:
- 生物化学和分子生物学
- 核酸化学的核酸化学
- 计算化学计算化学
背景情况:
- 由于二价阳离子度低,DNA酶10-23 (Dz10-23) 在体内有效性有限.
- 研究了对催化循环的修改,以在生理条件下增强Dz10-23的活性.
研究的目的:
- 为了研究5'S或5'R 5',8-cyclo-2'deoxyadenosine (cdA) 替代在催化循环中的对Dz10-23活性的影响.
- 使用计算方法阐明改变DNA酶活性的结构和电子基础.
主要方法:
- 使用放射性标记RNA测量DNA酶活性.
- 密度功能紧密结合 (DFTB) 方法,具有自我一致的电荷再分配,用于理论分析.
主要成果:
- 在催化循环中用cDA替换2'-脱氧腺素会降低DNA酶的活性.
- 抑制取决于cda修饰的位置和绝对配置.
- 理论研究表明,RcdA5替代增加了催化循环刚度,可能阻碍Me2+结合和最佳活性.
结论:
- 将cda纳入dz10-23的催化循环通常会降低催化活性.
- cdA的位置和立体化学显著影响抑制程度.
- 随着RcdA5的观察,催化循环的刚性增加是减少DNA酶功能的关键因素.
关键词:
8,5′-cyclo 2′-deoxyadenosine-deoxy-adenosine-deoxy-adenosine-deoxy-adenosine. 8,5′-cyclo 2′-deoxyadenosine-deoxy-adenosine-deoxy-adenosine-deoxy-adenosine. 8,5′-cyclo 2′-deoxy-adenosine-deoxy-adenosine-deoxy-deoxy-adenosine-deoxy-deoxy-deoxy-adenosine. 8,5′-cyclo 2′-deoxy-deoxy-adenosine-deoxy-deoxy-deoxy-deoxy-deoxy-deoxy-deoxy-deoxy-deoxy-deoxy-deoxy-deoxy-deoxy-deoxy-deoxy-deoxy造成的DNA损伤是DNA损伤.DNA酶 10-23 的使用情况.催化 DNA DNA 的作用.分子动力学分子动力学
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