Determining the effects of lipophilic drugs on membrane structure by solid-state NMR spectroscopy: the case of the antioxidant curcumin.
Determining the effects of lipophilic drugs on membrane structure by solid-state NMR spectroscopy: the case of the antioxidant curcumin.
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DOI：
10.1021/ja809217u
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发表时间：
2009-04-01
影响因子：
15
通讯作者：
Ramamoorthy A
中科院分区：
文献类型：
--
作者：
Barry J;Fritz M;Brender JR;Smith PE;Lee DK;Ramamoorthy A
姜黄素是姜黄粉的活性成分，姜黄粉是一种世代相传的传统药物中使用的天然香料。姜黄素具有广谱的抗氧化、抗癌、抗突变和抗炎特性，使其对于药物化合物的开发特别有意义。由于姜黄素对许多不相关的膜蛋白的功能有多种影响，有人认为它会影响双层本身的特性。然而，尚未尝试对姜黄素与膜的相互作用进行详细的原子水平研究。固态核磁共振和差示扫描量热实验相结合表明，姜黄素在低浓度下对膜结构具有很强的影响。姜黄素以跨双层方向深入插入膜中，通过氢键以类似于胆固醇的方式与脂质的磷酸基团锚定。与胆固醇一样，姜黄素诱导膜中的节段排序。对 NMR 结果得出的有序参数分布的浓度依赖性分析表明，姜黄素在膜中形成更高阶的寡聚结构，该结构跨越双层并可能使双层变薄。姜黄素促进高度弯曲的倒六边形相的形成，这可能影响细胞内的胞吐和膜融合过程。这里概述的实验表明有希望了解其他药物（例如辣椒素）的作用，其中药物诱导的膜结构改变具有很强的药理作用。
Curcumin is the active ingredient of the turmeric powder, a natural spice used for generations in traditional medicines. Curcumin’s broad spectrum of anti-oxidant, anti-carcinogenic, anti-mutagenic, and anti-inflammatory properties makes it particularly interesting for the development of pharmaceutical compounds. Due to curcumin’s various effects on the function of numerous unrelated membrane proteins, it has been suggested that it affects the properties of the bilayer itself. However, a detailed atomic-level study of the interaction of curcumin with membranes has not been attempted. A combination of solid-state NMR and differential scanning calorimetry experiments shows curcumin has a strong effect on membrane structure at low concentrations. Curcumin inserts deep into the membrane in a transbilayer orientation, anchored by hydrogen bonding to the phosphate group of lipids in a manner analogous to cholesterol. Like cholesterol, curcumin induces segmental ordering in the membrane. Analysis of the concentration dependence of the order parameter profile derived from NMR results suggests curcumin forms higher order oligomeric structures in the membrane that span and likely thin the bilayer. Curcumin promotes the formation of the highly curved inverted hexagonal phase which may influence exocytotic and membrane fusion processes within the cell. The experiments outlined here show promise for understanding the action of other drugs such as capsaicin in which drug-induced alterations of membrane structure have strong pharmacological effects.
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影响因子：
4.7
作者：
Hafner-Bratkovic, Iva;Gaspersic, Jernej;Jerala, Roman
通讯作者：
Jerala, Roman
影响因子：
3.5
作者：
Gardikis, Kostantinos;Hatziantoniou, Sophia;Demetzos, Costas
通讯作者：
Demetzos, Costas
影响因子：
6.1
作者：
Began, G;Sudharshan, E;Rao, AGA
通讯作者：
Rao, AGA
DOI：
10.1046/j.0014-2956.2001.02589.x
发表时间：
2001-12-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Bilmen, JG;Khan, SZ;Michelangeli, F
通讯作者：
Michelangeli, F
影响因子：
15
作者：
Dvinskikh, Sergey;Durr, Ulrich;Ramamoorthy, Ayyalusamy
通讯作者：
Ramamoorthy, Ayyalusamy