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Supramolecular organization of α-galactosylceramide in pure dispersions and in cationic DODAB bilayers.
Chemistry and Physics of Lipids ( IF 3.4 ) Pub Date : 2020-09-01 , DOI: 10.1016/j.chemphyslip.2020.104963
Letícia S Martins 1 , Evandro L Duarte 2 , M Teresa Lamy 2 , Julio H K Rozenfeld 1
Affiliation  

α-galactosylceramide (α-GalCer; KRN7000) strongly stimulates NKT cells. The structures of α-GalCer assemblies and of cationic DODAB bilayers containing α-GalCer were investigated by differential scanning calorimetry (DSC) and electron spin resonance (ESR) spectroscopy. Assemblies of α-GalCer have a very tightly packed gel phase, causing spin labels to cluster and display spin exchange interactions. An endothermic phase transition is observed by DSC, leading to a fluid phase. This phase transition peak disappears upon mixing with DODAB, showing that up to 9 mol% α-GalCer is miscible with the cationic lipid. ESR spectra show that α-GalCer decreases DODAB gel phase packing, resulting in a decrease of gel-fluid transition temperature and cooperativity in DSC thermograms of mixed bilayers. In contrast, α-GalCer increases the rigidity of the fluid phase. These effects are probably due to the conformation of the rigid amide bond that connects the phytosphingosine base of α-GalCer to its long and saturated acyl chain. Possibly, α-GalCer adopts a V-shaped conformation because of the perpendicular orientation of the amide bond towards the axes of the hydrocarbon chains. Apparently, the effect of the amide bond configuration is a key structural feature for the interaction between ceramide-based glycolipids and DODAB molecules, since we have previously reported a similar decrease of gel phase packing and increase in fluid phase rigidity for DODAB bilayers containing C24:1β-glucosylceramide. Since the structure of delivery systems is critical to the biological activity of α-GalCer, this work certainly contributes to the planning and development of novel immunotherapeutic tools.



中文翻译:

纯分散体和阳离子DODAB双层中的α-半乳糖基神经酰胺的超分子组织。

α-半乳糖神经酰胺(α-GalCer; KRN7000)强烈刺激NKT细胞。通过差示扫描量热法(DSC)和电子自旋共振(ESR)光谱研究了α-GalCer组件和包含α-GalCer的阳离子DODAB双层的结构。α-GalCer的装配体具有非常紧密的凝胶相,导致自旋标记聚集并显示自旋交换相互作用。DSC观察到吸热相变,导致流体相。与DODAB混合后,该相变峰消失,表明高达9 mol%的α-GalCer可与阳离子脂质混溶。ESR谱显示,α-GalCer降低了DODAB凝胶相的堆积,导致混合双层DSC热分析图中的凝胶-流体转变温度和协同性降低。相反,α-GalCer增加了液相的刚性。这些作用可能是由于将α-GalCer的植物鞘氨醇碱基与其长且饱和的酰基链相连的刚性酰胺键的构象所致。由于酰胺键朝向烃链轴的垂直方向,α-GalCer可能采用V形构象。显然,酰胺键构型的影响是基于神经酰胺的糖脂和DODAB分子之间相互作用的关键结构特征,因为我们之前已经报道了含有C24的DODAB双层的凝胶相堆积减少和液相刚性增加: 1β-葡萄糖基神经酰胺。由于递送系统的结构对于α-GalCer的生物学活性至关重要,因此这项工作无疑有助于新型免疫治疗工具的规划和开发。

更新日期:2020-09-10
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