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通过bis环闭合转化合成合的α-螺旋
Gerard J Hilinski1, Young-Woo Kim, Jooyeon Hong
1Department of Chemistry and Chemical Biology and Department of Stem Cell and Regenerative Biology, Harvard University , Cambridge, Massachusetts 02138, United States.
Journal of the American Chemical Society
|August 9, 2014
概括
研究人员使用双环闭合转化酶开发了"合",以提高稳定性和细胞透率. 这种新的稳定技术提高了类似药物的特性和细胞内传递潜力.
科学领域:
- 生物化学 生物化学
- 药用化学 医学化学
- 结构生物学 结构生物学
背景情况:
- 形状稳定的α-螺旋可以抑制蛋白质-蛋白质相互作用.
- 之前的工作利用单一的碳化合物基质通过环闭转化来增强性质.
研究的目的:
- 开发改进的方法来稳定生物活性构成中的α-螺旋.
- 为了探索具有多个连续主食的的特性.
主要方法:
- 双环闭合转化反应产生多级.
- 循环二重化谱学,核磁共振和用于结构研究的计算分析.
- 素蛋白解析测定,FACS和共聚焦显微镜用于稳定性和细胞透度的评估.
主要成果:
- 有效和选择性的双环闭合转化产生了具有多个连续主和中央螺旋环结点的.
- 与单片相比,合具有显著的热稳定性和优越的结构刚性.
- 与接合剂相比,接合剂表现出增强的细胞透能力.
结论:
- 多技术显著提高了阿尔法螺旋的稳定性和细胞透性.
- 这种方法为改善类药物类似性质提供了一个有希望的策略.
- 拼接类具有蛋白质和寡核酸细胞内传递的潜力.
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