迪亚利乙烯胺酸可识别基因组促进体DNA G-四重复合体的并行构造
Jyotirmayee Dash1, Pravin S Shirude, Shang-Te Danny Hsu
1The University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
Journal of the American Chemical Society
|November 5, 2008
概括
双乙烯胺衍生物是强大的G-四重复结合分子. 这些灵活的连接体具有高亲和力,对G-四重复性比双重复性DNA具有选择性,并区分不同的四重复结构.
科学领域:
- 药用化学 医学化学
- 化学生物学 化学生物学
- 分子生物学分子生物学
背景情况:
- G-四重复结构是涉及各种生物过程的非正规DNA二次结构.
- 开发选择性向G-四重复DNA的小分子是药物发现的关键策略.
- 现有的G-四重复合联体通常具有平面芳香核,这限制了它们的结构多样性和结合方式.
研究的目的:
- 为了合成和描述新的bis-phenylethynyl amide衍生物作为潜在的G-四重复合结剂.
- 研究这些具有G-四重复DNA的新型配体的结合亲和性,选择性和构造性方面.
- 探索一种具有形状灵活性的新一类G-四重复合联体.
主要方法:
- 索诺加希拉合,水解和化学选择性胺合用于合成.
- 光共振能量转移 (FRET) 化试验用于约束性评估.
- 表面等离子体共振 (SPR),循环二元化 (CD) 和 (1) H核磁共振 (NMR) 谱学用于详细的表征.
主要成果:
- 高效的三步合成 bis-phenylethynyl 胺衍生物.
- 证明了强大的G-四重复结合亲和力.
- 对G-四重复性比双重复性DNA具有很好的选择性.
- 显示了分子内促进子四重复体之间的有前途的歧视.
- 识别了沟结合作为主要的识别机制,有利于并行四重复形状.
结论:
- 双乙烯胺衍生物代表了G-四重复DNA向的新和强大的支架.
- 这些配体的形状灵活性有助于它们的高亲和力和选择性.
- 这些发现为设计具有独特结合模式的选择性G-四重复合联体开辟了新的途径.
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