循环式罗-意米达聚胺针对安德罗基因反应元件
David M Chenoweth1, Daniel A Harki, John W Phillips
1Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Journal of the American Chemical Society
|May 6, 2009
概括
循环罗-意米达 (Py-Im) 聚胺为基因调节提供了一种新的方法. 这些细胞透分子表现出高亲和度DNA结合,并有效调节基因表达,在治疗应用中显示出前景.
科学领域:
- 药用化学 医学化学
- 分子生物学分子生物学
- 有机合成 有机合成
背景情况:
- 罗-胺醇 (Py-Im) 聚胺是细胞透的DNA结合分子.
- 它们可以破坏转录因子-DNA相互作用并调节基因表达.
- 循环聚胺是一种研究较少的建筑,面临着合成的挑战.
研究的目的:
- 开发一种高产量的循环聚胺的合成.
- 研究新型循环Py-Im聚胺的DNA结合特性和基因调节效应.
- 针对雄激素反应元件 (ARE) 和雄激素受体 (AR) 途径.
主要方法:
- 对循环聚胺应用的溶液相合成方法.
- 高产量的循环化步骤,以改善合成可访问性.
- 针对5'-WGWWCW-3'序列的周期性8环Py-Im聚胺的表征.
主要成果:
- 通过改进的循环化方法,成功合成了循环的8环Py-Im聚胺1-3-3.
- 对于目标ARE序列的DNA结合 afinities 证明非常高.
- 在细胞培养中观察到AR基因的调节,表明细胞透性.
结论:
- 循环Py-Im聚胺可以使用开发的方法有效地合成.
- 这些循环聚胺表现出强大的DNA结合和基因调节活动.
- 循环结构增强了细胞透性和基因调节的治疗潜力.
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