有机金属乙烯胺复合物与核酸的高度选择性结合:新的识别机制
Haimei Chen1, John A Parkinson, Robert E Morris
1Department of Chemistry, University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, United Kingdom.
Journal of the American Chemical Society
|January 8, 2003
概括
(II) 烯抗癌复合物对核酸具有很高的选择性,优先结合瓜诺辛 (G) 而不是腺 (A). 这种受复杂结构影响的位点选择性有助于设计向的抗癌剂和DNA修饰试剂.
科学领域:
- 有机金属化学 有机金属化学
- 药用化学 医学化学
- 生物化学 生物化学
背景情况:
- (II) 烯复合体正在研究抗癌性质.
- 了解它们与核酸的相互作用对于药物设计至关重要.
研究的目的:
- 研究有机金属 ((II) 烯) 抗癌复合物的核酸衍生物的识别和结合.
- 阐明这些复合体对核基和核酸的位置选择性.
主要方法:
- 利用NMR光谱学 ((1) H, (31) P和 (15) N) 来研究相互作用.
- 研究了与各种核酸和核酸的结合 afinities 和反应动力学.
主要成果:
- (II) 复合物具有很高的选择性,优先结合于N7处的瓜诺辛 (G),N7处的伊诺辛 (I) 和N3处的蒂米丁 (T).
- 与 (II) 复合物相比,G和A基之间有较大的区别.
- 单核酸体表现出5'-酸盐结合,而循环核酸体则没有与基基结合.
- 反应速率受到烯配体和离开组 (Cl ((-) 或H ((2) O) 的影响.
结论:
- 位点选择性是由乙烯胺 (en) NH(2) 组的键和联体的疏水相互作用决定的.
- 这些发现为Ru arene复合体核酸识别的机制提供了洞察力.
- 这些知识可以指导开发更有效的抗癌药物和特定部位的DNA试剂.
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