一个RNA内部循环的快速交叉链接由抗癌药物西斯普拉丁
Alethia A Hostetter1, Erich G Chapman, Victoria J DeRose
1Department of Chemistry, University of Oregon, Eugene, Oregon 97403, USA.
Journal of the American Chemical Society
|July 2, 2009
概括
西斯是一种 (II) 抗癌药物,可以在复杂的RNA内部循环中交叉链接瓜基. 这种RNA交叉链接比DNA更快地发生,对RNA依赖的生物过程有影响.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 药用化学 医学化学
背景情况:
- 西斯是一种关键的 (II) 抗瘤药物,向基因组DNA.
- 与RNA的相互作用,特别是像结合体RNA这样的复杂结构,比其DNA相互作用更难理解.
研究的目的:
- 为了研究思丁与结构复杂的RNA内部循环的反应.
- 描述思普拉丁在RNA中形成交叉链的潜力.
主要方法:
- 研究了西斯普拉丁与来自U2:U6结合体RNA的41核酸RNA子域 (BBD) 之间的反应.
- 使用有限的性水解来识别交叉链接的瓜残留物.
- 使用UV-Vis光谱在受控的离子环境中研究反应动力学.
- 使用MALDI-MS来证实生物化学发现.
主要成果:
- 齐斯普拉丁通过与相反的关氨基基结合,在BBDRNA内部循环中形成分子内交叉链接.
- BBD RNA和相关的RNA发针与cisplatin的反应速度比DNA发针类似物快5-6倍.
- 速率常量表明,与DNA相比,思丁与RNA的结合速度明显更快.
- MALDI-MS数据支持一个竞争金结合点模型.
结论:
- 西斯普拉丁可以诱导复杂的RNA结构中的内部循环和其他不寻常的交叉链接.
- 西斯-RNA交叉链接的动力学与生物时间尺度有关.
- 这些发现突显了西斯在依赖RNA的细胞过程中的潜在非目标效应.
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