测试使用合成循环二聚体合成的被动膜透性的构造假设
Taha Rezai1, Bin Yu, Glenn L Millhauser
1Department of Chemistry and Biochemistry, University of California, Santa Cruz, 95064, USA.
Journal of the American Chemical Society
|February 24, 2006
概括
分子构造显著影响被动膜扩散. 循环酸中的分子内键增强了膜的透性,其中一个二聚体呈现的速率与环素A相似.
科学领域:
- 生物化学 生物化学
- 物理化学 物理化学
- 药理学 药理学是指药理学的学科.
背景情况:
- 对小分子被动膜扩散的 conformational 效应仍然不太了解.
- 假设分子内键,特别是涉及胺N-H组,可以降低溶解成本并增强扩散.
- 研究循环二聚体可以阐明构造在膜运输中的作用.
研究的目的:
- 为了测试内部分子键影响被动膜扩散速率的假设.
- 描述不同形状的循环二聚体的膜扩散.
- 为了将形状性质与观察到的扩散率相关联.
主要方法:
- 基于cyclo[Leu-Leu-Leu-Leu-Pro-Tyr]的循环六二聚体的合成和表征.
- 测量已识别的双立体体的被动膜扩散速率.
- 溶液核磁共振 (NMR) 研究和/ (H/D) 交换实验,以评估分子内键和动态.
主要成果:
- 两个循环六二聚体在被动膜扩散速率上表现出2个日志单位的差异.
- 在膜扩散率和分子内键的程度之间观察到强烈的相关性.
- 更快的H/D交换率与更高的膜透性相关.
结论:
- 形状,特别是分子内结的程度,是小分子被动膜扩散的关键决定因素.
- 最透的二聚体,cyclo[d-Leu-d-Leu-d-Leu-Pro-Tyr],表现出与口服药物cyclosporine A.相比的被动膜扩散.
- 这项研究为改善膜传输的分子设计提供了宝贵的见解,这与药物开发有关.
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