基于聚烯螺旋架构的细胞透剂
Yannick A Fillon1, Jason P Anderson, Jean Chmielewski
1Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, USA.
Journal of the American Chemical Society
|August 18, 2005
概括
基于聚烯螺旋结构的新型细胞透剂显示显著增强细胞吸收. 这些两性药物,特别是那些含有关尼基的药物,性能优于柔性和TAT,毒性最小.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 药物运输 药物运输 药物运输
背景情况:
- 细胞透 (CPP) 对于将分子送入细胞至关重要.
- 设计具有增强疗效和特异性的CPP仍然是一个挑战.
- 聚二烯 (PPII) 螺旋为设计提供了一个独特的结构支架.
研究的目的:
- 设计和合成使用聚烯螺旋 (PPII) 架构的新型细胞透剂.
- 为了研究两性和阴阳电荷在细胞吸收中的作用.
- 为了比较这些新型药物的疗效与现有的CPPs,如Tat.
主要方法:
- 合成基于的两性聚烯螺旋剂,含有有 (,氨) 和疏水的部分.
- 循环二元化 (CD) 光谱测试以确认PPII螺旋结构.
- 细胞吸收研究使用MCF-7细胞来量化药物内部化.
- 细胞毒性测试用于评估安全性.
主要成果:
- 设计的PPII螺旋剂保持了它们的骨干结构.
- 具有多个guanidinium组的药物在MCF-7细胞中显著增加了细胞吸收.
- 两性对增强细胞转移至关重要;编码版本的效果不那么好.
- 最强效的药物P11LRR的细胞吸收量几乎是Tat的十倍,细胞毒性最小.
结论:
- 两胞性PPII螺旋结构可以有效地被设计为强大的细胞透剂.
- 与含氨酸或柔性对应物相比,富含关氨的PPII螺旋体表现出较高的细胞吸收率.
- 这些发现突出了治疗应用的有希望的新型CPP类.
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