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特定氘代神经酰胺[AP]-C18的合成及其利用中子衍射的生物物理特性分析

Synthesis of specifically deuterated ceramide [AP]-C18 and its biophysical characterization using neutron diffraction.

作者信息

Sonnenberger Stefan, Eichner Adina, Hauß Thomas, Schroeter Annett, Neubert Reinhard H H, Dobner Bodo

机构信息

Institute of Pharmacy, Martin Luther University Halle-Wittenberg, 06120 Halle/Saale, Germany.

Institute of Soft Matter and Functional Materials, Helmholtz-Zentrum Berlin für Materialien und Energie, 14109 Berlin, Germany.

出版信息

Chem Phys Lipids. 2017 Apr;204:15-24. doi: 10.1016/j.chemphyslip.2017.02.001. Epub 2017 Feb 12.

Abstract

The very heterogeneous group of ceramides is known to be mandatory for proper barrier functions of the outermost layer of mammalian skin, referred to as stratum corneum (SC). The synthesis of a specifically deuterated ceramide [AP]-C18 variant is described. The synthesized ceramide contains the racemic forms of the α hydroxy fatty acid. For the biophysical implementation, the received diastereomeric ceramide was applied in a neutron diffraction experiment. Therefore, a SC lipid model membrane was prepared containing the described ceramide (CER), cholesterol (CHOL), stearic acid (SA), and cholesterol sulfate (ChS) in a ratio of 55/25/15/5wt%. Thus, we were able to localize the deuterated molecule part within the bilayers. In the process, a short-periodicity phase (SPP) was observed with a unit cell scale of about 44Å. For the first time, we were able to confirm former ideas concerning the arrangement of the CER within this quaternary lipid model membrane.

摘要

已知种类繁多的神经酰胺对于哺乳动物皮肤最外层(即角质层,SC)的正常屏障功能至关重要。本文描述了一种特定氘代神经酰胺[AP]-C18变体的合成。合成的神经酰胺包含α羟基脂肪酸的外消旋形式。为了进行生物物理研究,将得到的非对映体神经酰胺应用于中子衍射实验。因此,制备了一种SC脂质模型膜,其含有所述神经酰胺(CER)、胆固醇(CHOL)、硬脂酸(SA)和硫酸胆固醇(ChS),比例为55/25/15/5wt%。通过这种方式,我们能够将氘代分子部分定位在双层膜内。在此过程中,观察到一个短周期相(SPP),其晶胞尺度约为44Å。我们首次能够证实此前关于CER在这种四级脂质模型膜中排列方式的观点。

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