激素 - 树脂结合物的联结体可及性和生物活性取决于pH和pH历史
Sung Hoon Kim, Zeynep Madak-Erdogan, Sung Chul Bae1
1§IBS Center for Soft and Living Matter and UNIST, Ulsan 689-798, South Korea.
Journal of the American Chemical Society
|July 18, 2015
概括
当pH值下降时,雌激素 - 基结合物不可逆转地失去生物活性,因为结合物被困住. 这种依赖pH的活性损失对于设计使用聚胺胺 (PAMAM) 树脂体的新药输送系统至关重要.
科学领域:
- 生物结合化学
- 纳米医学
- 分子药理学
背景情况:
- 聚胺胺 (PAMAM) 树突可以与雌激素结合,对非基因组雌激素作用进行选择性调节.
- 雌激素 - 树突结合物 (EDC) 经历了依赖pH的形态变化,影响了连体的可访问性和生物活性.
研究的目的:
- 为了研究雌激素-基结合物 (EDC) 的pH依赖性行为和稳定性.
- 了解pH诱导的结构变化对EDC生物活性和连接物可访问性的影响.
主要方法:
- 使用光灭和时间解析的光异性学来研究TMR-PAMAM上的配体屏蔽.
- 使用动态核磁共振来分析PAMAM树突核中的联体封闭.
- 在pH循环后评估雌激素-PAMAM结合物的细胞刺激活性.
主要成果:
- 在PAMAM树枝体上,连体屏蔽在pH 7以上,在pH 7以下较低.
- 暴露于pH循环 (8. 5至4. 5和回8. 5) 的EDC显示细胞刺激活性不可逆转的损失.
- 动态核磁共振显示,在较低的pH值下,荷尔蒙配体在疏水性树突核中被封闭.
结论:
- 雌激素 - 树突结合物的活性状态是转移稳定的,对pH值的变化敏感.
- 由于pH诱导的连接体封闭,不可逆转的活性掩盖是设计基于PAMAM树突的药物合物的重要考虑因素.
- 这些发现强调了纳米载体系统在药物输送应用中的pH稳定性的重要性.
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