通过从分子动力学模拟的见解,揭示了皮与β-环氧及其甲基化衍生物的动态和热力学相互作用
Roya Gholami1, Khaled Azizi2,3, Mokhtar Ganjali Koli1,4
1Department of Chemistry, University of Kurdistan, Sanandaj, Iran.
Scientific reports
|May 31, 2024
概括
甲基化环极素 (CDs) 改善了皮 (HC) 的负载和稳定性. 不同的甲基化模式影响HC.
科学领域:
- 超分子化学 超分子化学
- 计算化学计算化学
- 制药科学 制药科学
背景情况:
- 环极素 (CD) 被广泛用于提高药物的稳定性和生物可用性.
- 甲基化环极素 (Me-CDs) 为药物封装提供了修改的特性.
- 皮 (HC) 是一种具有有限可溶性和稳定的皮质类固醇.
研究的目的:
- 研究皮 (HC) 与各种甲基化环极 (Me-CD) 衍生物之间的相互作用机制.
- 了解甲基化程度和位置如何影响HC加载和封装.
- 评估甲基化对CD及其与HC复合物的结构和动态性质的影响.
主要方法:
- 用分子动力学 (MD) 模拟来研究HC-Me-CD相互作用.
- 分析包括灵活性的平方根平均波动 (RMSF),含水量的辐射分布函数 (RDF) 和CD边框的结构分析.
- 计算了结合的自由能量和相互作用能量来评估结合的亲和力.
主要成果:
- HC加载机制因甲基化模式而异,影响了CD腔内的方向.
- 甲基化增加了CD的灵活性,但与HC的复杂化导致灵活性降低,增强稳定性.
- Me-CD显示极性下降,并释放了高能水分子,促进了HC加载.
- 对Me-CDs的HC结合在热力学上比对本源βCD更有利,特定衍生物显示最强的关联.
结论:
- 甲基化显著改变了环极素与皮的相互作用.
- 特定的甲基化环极素,如6-MeβCD,2-MeβCD和2,3-D-MeβCD,显示出对HC的优越结合亲和力和封装效率.
- 这些发现为设计使用修改后的环氧素的先进药物输送系统提供了宝贵的见解.
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