首页> 外文期刊>Biochimica et biophysica acta. Biomembranes >New insights into the influence of monofluorination on dimyristoylphosphatidylcholine membrane properties: A solid-state NMR study
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New insights into the influence of monofluorination on dimyristoylphosphatidylcholine membrane properties: A solid-state NMR study

机译:单氟化对二巯基磷脂酰胆碱膜特性的新见解:固态NMR研究

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Solid-state F-19 NMR spectroscopy is a method of choice to study the interactions between lipid membranes and other molecules such as peptides, proteins or drugs. Numerous fluorine-labeled NMR probes have been developed over the last few years, especially fluorine-labeled peptides. In order to develop a new kind of NMR reporter molecule and a complementary approach to fluorine-labeling of peptides, we synthesized six mono fluorinated derivatives of the lipid dimyristoylphosphatidylcholine (F-DMPC), with the fluorine atom located along the acyl chain linked to the central glycerol position. To better understand the behavior of these fluorine labeled lipids, we report here the investigation of F-DMPC membrane properties using solid-state H-2, N-15, F-19 and P-31-NMR spectroscopy. This study was carried out on pure F-DMPC bilayers as well as F-DMPC/DMPC mixtures at various ratios. Slight perturbations were observed for pure F-DMPC multilamellar vesicles (MLVs), most noticeable for lipids with the fluorine atom located at the extremities of the acyl chain. On the other hand, no significant perturbations were observed for F-DMPC/DMPC MLVs containing up to 25% F-DMPC, nor for any fluorine-labeled bilayers that were prepared as macroscopically oriented samples. To test the interaction with some representative peptides, N-15-labeled alpha-helical antimicrobial peptides (AMPs) were incorporated into F-DMPC/DMPC (1/3) bilayers. N-15 SS-NMR analyses confirmed that the known orientation of each AMP in pure DMPC was preserved in the presence of 25% monofluorinated DMPC, irrespective of the position of the F-19-label. In summary, F-DMPC/DMPC (1/3) model membranes can be used as NMR reporter to study membrane interactions with other molecules.
机译:固态F-19 NMR光谱是研究脂膜与其他分子(如肽,蛋白质或药物)之间的相互作用的方法。在过去几年中开发了许多氟标记的NMR探针,尤其是氟标记的肽。为了开发一种新的NMR报告分子和氟肽氟标记的互补方法,我们合成了脂质二巯基磷脂酰氨基氨基(F-DMPC)的六种单氟化衍生物,氟原子沿着与之连接的酰基链中央甘油位置。为了更好地理解这些氟标记的脂质的行为,我们在此报告使用固态H-2,N-15,F-19和P-31-NMR光谱研究F-DMPC膜性能。该研究在纯F-DMPC双层以及以各种比率进行纯F-DMPC双层以及F-DMPC / DMPC混合物进行。针对纯F-DMPC多硅囊泡(MLV)观察到轻微的扰动,对于位于酰基链的末端的氟原子,最明显的脂质。另一方面,对于含有高达25%F-DMPC的F-DMPC / DMPC MLV,没有针对宏观定向样品制备的任何氟标记的双层的F-DMPC / DMPC MLV没有显着的扰动。为了测试与一些代表性肽的相互作用,将N-15标记的α-螺旋抗微生物肽(AMPs)掺入F-DMPC / DMPC(1/3)双层中。 N-15SS-NMR分析证实,在25%单氟化DMPC的存在下,保留了每种放大器在纯DMPC中的已知取向,而不管F-19标签的位置如何。总之,F-DMPC / DMPC(1/3)模型膜可用作NMR报告者,以研究与其他分子的膜相互作用。

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