多部位化:一种可调节,可逆的策略,以定制治疗来提供治疗
Mark S Bannon1, Jeffrey F Ellena2, Aditi S Gourishankar1
1Department of Chemical Engineering, University of Virginia Charlottesville VA 22903 USA rl2qm@virginia.edu +1 434 243 3628.
概括
化治疗性可以增强细胞膜的透性. 在αCT11上修改的数量和位置会影响疏水性和水解,从而使可调节的分泌成为可能.
科学领域:
- 药用化学 医学化学
- 生物化学 生物化学
- 分子工程分子工程分子工程
背景情况:
- 治疗性具有前景,但由于细胞膜透性较低,面临交付挑战.
- 阳离子的化可以改善对细胞内的疏水性和细胞内化.
研究的目的:
- 调查治疗性胺αCT11上的基修饰的数量和位置如何影响其疏水性和水解.
- 提供分子工程洞察力,以优化化化策略.
主要方法:
- 费舍尔化用于将甲基安装到αCT11上.
- 用2DNMR,HPLC和质谱分析产品,以确定化部位和疏水性.
- 监测了水解速率和机制,包括阿斯巴尔提胺的形成.
主要成果:
- 隔离了五种不同的化αCT11产品,其水性有所增加.
- 在C端异黄素的化产生了最大的疏水性增加.
- 水解稳定性各不相同,C端异黄素 Ester最稳定,其次是谷氨酸,而酸 Esters迅速水解,形成过渡性阿斯巴提胺.
结论:
- 治疗性的多部位化是一种可调和可逆的策略,用于增强细胞输送.
- 了解位对疏水性和水解的影响对于设计有效的疗法至关重要.
- 实验室研究表明,用化αCT11改善了细胞迁移,验证了该方法.
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