Department of Chemistry and Biochemistry and Biomolecular Sciences Institute, Florida International University, 11200 SW Eighth Street, Miami, Florida 33199, United States.
Translational Glycobiology Institute, Department of Translational Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW Eighth Street, Miami, Florida 33199, United States.
J Phys Chem B. 2024 Sep 19;128(37):8869-8877. doi: 10.1021/acs.jpcb.4c02696. Epub 2024 Sep 3.
Fucosylated carbohydrate antigens play critical roles in physiology and pathology with function linked to their structural details. However, the separation and structural characterization of isomeric fucosylated epitopes remain challenging analytically. Here, we report for the first time the influence of alkali metal cations (Li, Na, K, Rb, and Cs) and halogen anions (Cl, Br, and I) on the gas-phase conformational landscapes of common fucosylated trisaccharides (Lewis A, X, and H types 1 and 2) and tetrasaccharides (Lewis B and Y) using trapped ion mobility spectrometry coupled to mass spectrometry and theoretical calculations. Inspection of the mobility profiles of individual standards showed a dependence on the number of mobility bands with the oligosaccharide and the alkali metal and halogen; collision cross sections are reported for all of the observed species. Results showed that trisaccharides (Lewis A, X, and H types 1 and 2) can be best mobility resolved in the positive mode using the [M + Li] molecular ion form (baseline resolution r ≈ 2.88 between Lewis X and A); tetrasaccharides can be best mobility resolved in the negative mode using the [M + I] molecular ion form (baseline separation ≈ 1.35 between Lewis B and Y). The correlation between the number of oligosaccharide conformers as a function of the molecular ion adduct was studied using density functional theory. Theoretical calculations revealed that smaller cations can form more stable structures based on the number of coordinations, while larger cations induced greater oligosaccharide reorganizations; candidate structures are proposed to better understand the gas-phase oligosaccharide rearrangement trends. Inspection of the candidate structures suggests that the interplay between ion size/charge density and molecular structure dictated the conformational preferences and, consequently, the number of mobility bands and the mobility separation across isomers. This work provides a fundamental understanding of the gas-phase structural dynamics of fucosylated oligosaccharides and their interaction with alkali metals and halogens.
岩藻糖基碳水化合物抗原在生理和病理中发挥着关键作用，其功能与其结构细节相关。然而，具有立体异构的岩藻糖基表位的分离和结构特征仍然具有分析挑战性。在此，我们首次报道了碱金属阳离子（Li、Na、K、Rb 和 Cs）和卤素阴离子（Cl、Br 和 I）对常见岩藻糖基三糖（Lewis A、X 和 H 型 1 和 2）和四糖（Lewis B 和 Y）的气相构象景观的影响，方法是使用离子阱迁移谱与质谱和理论计算相结合。对单个标准品的迁移率谱进行检查，结果表明其依赖于迁移率带的数量与寡糖以及碱金属和卤素的数量有关；报道了所有观察到的物种的碰撞截面。结果表明，三糖（Lewis A、X 和 H 型 1 和 2）可以在正模式下使用[M+Li]分子离子形式（Lewis X 和 A 之间的基线分辨率 r ≈ 2.88）最佳地进行迁移率分辨；四糖可以在负模式下使用[M+I]分子离子形式（Lewis B 和 Y 之间的基线分离 ≈ 1.35）最佳地进行迁移率分辨。使用密度泛函理论研究了作为分子离子加合物函数的寡糖构象体数量之间的相关性。理论计算表明，基于配位数量，较小的阳离子可以形成更稳定的结构，而较大的阳离子会引起更大的寡糖重排；提出候选结构以更好地理解气相寡糖重排趋势。对候选结构的检查表明，离子大小/电荷密度与分子结构之间的相互作用决定了构象偏好，进而决定了迁移率带的数量和异构体之间的迁移率分离。这项工作为岩藻糖基寡糖的气相结构动力学及其与碱金属和卤素的相互作用提供了基本的理解。
