Complex Carbohydrate Research Center , University of Georgia , Athens , Georgia 30602 , United States.
J Org Chem. 2019 Feb 15;84(4):1706-1724. doi: 10.1021/acs.joc.8b01411. Epub 2019 Jan 29.
NMR studies of two C-labeled disaccharides and a tetrasaccharide were undertaken that comprise the backbone of a novel thermal hysteresis glycolipid containing a linear glycan sequence of alternating [βXyl p-(1→4)-βMan p-(1→4)] dimers. Experimental trans-glycoside NMR J-couplings, parameterized equations obtained from density functional theory (DFT) calculations, and an in-house circular statistics package ( MA'AT) were used to derive conformational models of linkage torsion angles ϕ and ψ in solution, which were compared to those obtained from molecular dynamics simulations. Modeling using different probability distribution functions showed that MA'AT models of ϕ in βMan(1→4)βXyl and βXyl(1→4)βMan linkages are very similar in the disaccharide building blocks, whereas MA'AT models of ψ differ. This pattern is conserved in the tetrasaccharide, showing that linkage context does not influence linkage geometry in this linear system. Good agreement was observed between the MA'AT and MD models of ψ with respect to mean values and circular standard deviations. Significant differences were observed for ϕ, indicating that revision of the force-field employed by GLYCAM is probably needed. Incorporation of the experimental models of ϕ and ψ into the backbone of an octasaccharide fragment leads to a helical amphipathic topography that may affect the thermal hysteresis properties of the glycolipid.
我们对两种 C 标记的二糖和一种四糖进行了 NMR 研究，这些二糖和四糖构成了一种新型热滞糖脂的骨架，该糖脂含有一个线性聚糖序列，由交替的 [βXyl p-(1→4)-βMan p-(1→4)] 二聚体组成。实验性的反糖苷 NMR J 耦合、从密度泛函理论（DFT）计算中获得的参数化方程以及内部的圆形统计软件包（MA'AT）用于推导溶液中键扭转角 ϕ 和 ψ 的构象模型，这些模型与分子动力学模拟得到的模型进行了比较。使用不同的概率分布函数进行建模表明，在二糖构建模块中，βMan(1→4)βXyl 和 βXyl(1→4)βMan 键的 MA'AT 模型在 ϕ 上非常相似，而 ψ 的 MA'AT 模型则不同。这种模式在四糖中得以保留，表明在这个线性系统中，键的上下文不会影响键的几何形状。MA'AT 和 MD 模型在 ψ 的平均值和圆形标准偏差方面表现出良好的一致性。在 ϕ 方面观察到显著差异，表明可能需要对 GLYCAM 所使用的力场进行修订。将 ϕ 和 ψ 的实验模型纳入八糖片段的骨架中，导致了一种具有螺旋两亲性拓扑的结构，这可能会影响糖脂的热滞性质。
