Cholesteryl-β-D-glucoside (ChoGlc) is a mammalian glycolipid that is expressed in brain tissue. The effects of glucosylation on the ordering and lipid interactions of cholesterol (Cho) were examined in membranes composed of N-stearoyl sphingomyelin (SSM), which is abundant in the brain, and to investigate the possible molecular mechanism involved in these interactions. Differential scanning calorimetry revealed that ChoGlc was miscible with SSM in a similar extent of Cho. Solid-state ²H NMR of deuterated SSM and fluorescent anisotropy using 1,6-diphenylhexatriene demonstrated that the glucosylation of Cho significantly reduced the effect of the sterol tetracyclic core on the ordering of SSM chains. The orientation of the sterol core was further examined by solid-state NMR analysis of deuterated and fluorinated ChoGlc analogues. ChoGlc had a smaller tilt angle between the long molecular axis (C3–C17) and the membrane normal than Cho in SSM bilayers, and the fluctuations in the tilt angle were largely unaffected by temperature-dependent mobility changes of SSM acyl chains. This orientation of the sterol core of ChoGlc leads to reduce sterol-SSM interactions. The MD simulation results suggested that the Glc moiety perturbs the SSM-sterol interactions, which reduces the umbrella effect of the phosphocholine headgroup because the hydrophilic glucose moiety resides at the same depth as an SSM amide group. These differences between ChoGlc and Cho also weaken the SSM-ChoGlc interactions. Thus, the distribution and localization of Cho and ChoGlc possibly control the stability of sphingomyelin-based domains that transiently occur at specific locations in biological membranes.

胆固醇-β-D-葡萄糖苷（ChoGlc）是在脑组织中表达的哺乳动物糖脂。在脑中富含N-硬脂酰鞘磷脂（SSM）的膜中检查了糖基化对胆固醇（Cho）有序和脂质相互作用的影响，并研究了参与这些相互作用的可能的分子机制。差示扫描量热法显示，ChoGlc在相似程度的Cho中可与SSM混溶。固态²氘代SSM的1 H NMR和使用1,6-二苯基己三烯的荧光各向异性表明，Cho的糖基化显着降低了固醇四环核对SSM链有序的影响。通过氘化和氟化的ChoGlc类似物的固态NMR分析进一步检查了甾醇核的取向。在SSM双层中，ChoGlc在长分子轴（C3-C17）与膜法线之间的倾斜角小于Cho，而倾斜角的波动在很大程度上不受SSM酰基链的温度依赖性迁移率变化的影响。ChoGlc的固醇核心的这种取向导致减少固醇-SSM相互作用。MD模拟结果表明，Glc部分干扰了SSM-固醇相互作用，由于亲水性葡萄糖部分与SSM酰胺基位于同一深度，因此这降低了磷酸胆碱头基的保护作用。ChoGlc和Cho之间的这些差异也削弱了SSM-ChoGlc的相互作用。因此，Cho和ChoGlc的分布和定位可能会控制基于鞘磷脂的结构域的稳定性，该结构域瞬时发生在生物膜的特定位置。