非类固醇抗炎药物与脂质膜的结构关联
Mohan Babu Boggara1, Mihaela Mihailescu, Ramanan Krishnamoorti
1Department of Chemical and Biomolecular Engineering, University of Houston, Houston, Texas 77204, United States.
Journal of the American Chemical Society
|November 9, 2012
概括
布洛芬是一种非类固醇抗炎药物,在脂双层中进行了研究. 中子衍射和模拟显示,带电的布洛芬存在于头组中,使双层变薄,而中性布洛芬则透得更深.
科学领域:
- 生物物理学的生物物理.
- 材料科学 材料科学 材料科学
- 药理学 药理学是指药理学的学科.
背景情况:
- 非类固醇抗炎药物 (NSAIDs) 广泛用于治疗疼痛和炎症.
- 无 NSAID 药物涉及治疗癌症和阿尔茨海默氏症等疾病.
- 胃肠道毒性是NSAIDs已知的副作用,其分子机制尚不清楚.
研究的目的:
- 为了确定ibuprofen在脂双层中的分子位置和分布.
- 为了研究布洛芬加入后脂质双层的结构变化.
- 在分子层面上阐明布洛芬与脂质二层的相互作用.
主要方法:
- 用对比差异的中子衍射来确定药物的位置.
- 用分子动力学 (MD) 模拟来补充衍射数据.
- 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) 脂质双层被用作一个模型系统.
主要成果:
- 充电型布洛芬局部存在于脂双层的极端头组区域.
- 布洛芬的结合导致了显著的双层稀释.
- 在药物存在时,观察到水分子与双层的相关性增加.
- MD模拟显示中性易布洛芬在低pH下,与其充电形式相比,在双层内更深地定位.
结论:
- 这项研究为ibuprofen-lipid双层相互作用提供了详细的结构见解.
- 这些发现表明NSAID诱导的膜变化的分子基础.
- 了解二层中药物的位置对于预测疗效和副作用至关重要.
相关概念视频
What are Lipids?
Lipids function as structural components of cellular membranes, in addition to acting as energy reservoirs and signaling molecules. They are thus crucial to all living organisms. The three biologically important classes of lipids are triglycerides, phospholipids, and steroids.
Non-Polar and Hydrophobic Characteristics of Lipids
Lipids are a structurally and functionally diverse group of hydrocarbons—compounds consisting of carbon and hydrogen atoms. The carbon-carbon and carbon-hydrogen bonds...
Non-Polar and Hydrophobic Characteristics of Lipids
Lipids are a structurally and functionally diverse group of hydrocarbons—compounds consisting of carbon and hydrogen atoms. The carbon-carbon and carbon-hydrogen bonds...
What are Lipids?
Overview
Structure of Lipids
Lipids include a diverse group of compounds that are largely nonpolar in nature. This is because they are hydrocarbons that include mostly nonpolar carbon-carbon or carbon-hydrogen bonds. Non-polar molecules are hydrophobic (“water fearing”), or insoluble in water. Lipids perform many different functions in a cell. Cells store energy for long-term use in the form of fats. Lipids also provide insulation from the environment for plants and animals. For example, they help keep aquatic birds and...
Structure of Lipids
Lipids include a diverse group of compounds that are largely nonpolar in nature. This is because they are hydrocarbons that include mostly nonpolar carbon-carbon or carbon-hydrogen bonds. Non-polar molecules are hydrophobic (“water fearing”), or insoluble in water. Lipids perform many different functions in a cell. Cells store energy for long-term use in the form of fats. Lipids also provide insulation from the environment for plants and animals. For example, they help keep aquatic birds and...
Structure of Lipids
Lipids include a diverse group of compounds that are largely nonpolar in nature. This is because they are hydrocarbons that include mostly nonpolar carbon-carbon or carbon-hydrogen bonds. Non-polar molecules are hydrophobic (“water fearing”), or insoluble in water. Lipids perform many different functions in a cell. Cells store energy for long-term use in the form of fats. Lipids also provide insulation from the environment for plants and animals. For example, they help keep aquatic birds and...
Assembly of the Lipid Bilayer in the ER
Biological membranes are more than just a barrier separating cell cytoplasm from the outside environment. They are highly dynamic and help maintain the integrity and physiological stability of the cells as well as membrane-bound organelles. Membranes also play vital roles in cell-to-cell and intracellular communication.
A large chunk of any biological membrane is composed of phospholipids. These lipids have a heterogeneous distribution across different subcellular organelles and even between...
A large chunk of any biological membrane is composed of phospholipids. These lipids have a heterogeneous distribution across different subcellular organelles and even between...


