通过DNA间隔,可促进向DNA的有效共价结合
Ali A Almaqwashi1, Wen Zhou2,3, M Nabuan Naufer4
1Physics Department , King Abdulaziz University , Rabigh 21911 , Saudi Arabia.
Journal of the American Chemical Society
|January 3, 2019
概括
甲是一种抗癌药物,通过两步过程快速结合DNA. 这种机制与其同位素不同,能够有效地定位DNA.
科学领域:
- 生物化学
- 分子生物学
- 化学生物学
背景情况:
- 甲是一种单一功能抗癌药物.
- 它表现出比西斯更快的DNA共价结合活性.
- 它的DNA结合的分子机制尚未完全理解.
研究的目的:
- 为了阐明DNA结合的分子机制.
- 为了比较甲与其立体同位素及其相关化合物的DNA结合动力学.
- 研究几何形状和连接体大小在DNA结合中的作用.
主要方法:
- 使用光学子进行单分子研究.
- 监测单个λ-DNA分子的时间依赖扩展.
- 对DNA化合物结合和分离的动态分析.
主要成果:
- 甲与DNA的结合发生在两个阶段:快速的可逆延长 (τ ≈10秒),随后是缓慢的不可逆延长 (∼30分钟).
- 立体异构体转三甲仅显示了快速,可逆的延长.
- 由于缺乏氨酸连接体,氨酸不会导致DNA解,这表明氨酸组的重要性.
结论:
- 甲的DNA结合机制涉及快速的合,随后是缓慢的共价结合.
- 在不可逆转的DNA共价结合中, cis 配置至关重要.
- 可逆的DNA间隔作用作为不可逆的DNA-Pt结合的过渡状态.
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