Hopping Sugars: molecular mechanism of protonatedglycans rearrangement

跳糖：质子化糖链的分子机制 重排 马特乌兹·马里安斯基 摘要 碳水化合物是三类重要的生物聚合物之一，参与了 一系列的生物过程。它们的多种功能都是由一名高空潜水员促进的- 多糖分子结构的强度和适应性，它有效地构成了 糖苷分析方法面临的一个主要挑战。质谱学分析 (MS)方法通常因分子-糖链重排而变得复杂。 LAR机制仍未确定。 为了分析结构前提条件并确定分子机制- 在重新安排的基础上，我将设计简化的采样方案 能够同时筛选构象(在一个拓扑内)和结构(BE- 在不同的离子拓扑之间)空间。密度泛函理论方法能够 将糖链序列和带电糖链的三维结构连接起来，能够 预测热力学稳定重排产物并提出设想 分子机制。 接下来，采样方案将被应用于低聚糖集合 已观察到遵循不同机制的糖链重排。甘油- Can包括小Lewis A和Y抗原及其唾液酸化的岩藻糖迁移 形式，和更大的双天线N-糖链。此外，这些甘氨酸的结构空间- 将探索罐头，包括替代的充分体，以量化结构先决条件- 管理该机制的网站。拟议的暂定反应机理将是 与波士顿大学林博士合作在串联MS实验中进行测试 医学院。 该提案建议从解释性角色向探索性角色的范式转变- 描述多糖的理论方法。实际上，全面理解 糖链的结构空间将在多个构象出现时发光 离子迁移率光谱中的系综，将有助于预测和Red-fl错误 以气相为基础的糖分析中的峰。 1

Hopping sugars: molecular mechanism of protonated glycans rearrangement Mateusz Marianski Abstract Carbohydrates, one of the three important classes of biopolymers, are involved in a range of biological processes. Their multiple functions are facilitated by a high diver- sity and adaptability of the glycan's molecular structure which, effectively, constitutes a major challenge for glycoanalitic methods. The analysis by mass-spectroscopy (MS) methods is often complicated by glycan rearrangements for which the molecu- lar mechanism remains undetermined. In order to analyze structural prerequisites and determine the molecular mech- anism underpinning the rearrangement, I will design streamlined sampling protocol that is able to screen both conformational (within one topology) and structural (be- tween varying ion topologies) space. The density-functional theory methods are able to link a glycan sequence and 3-dimensional structure of charged glycans, are able to predict thermodynamically stable rearrangement products and propose tentative molecular mechanism. The sampling protocol will be next applied to set of oligosaccharides for which glycan rearrangements, following different mechanism, has been observed. The gly- cans include fucose migration in small Lewis A and Y antigens and their sialylated forms, and larger biantennary N-glycan. Moreover, the structural space of these gly- cans, including alternative epimers, will be explored to quantify structural prerequi- sites governing the mechanism. The proposed tentative reaction mechanism will be tested in tandem MS experiments with collaboration with Dr. Lin at Boston University Medical School. The proposal suggest a paradigm shift from explanatory to exploratory role of the- oretical methods in describing the glycans. In effect, comprehensive understanding of glycans structural space will shed lights on occurrence of multiple conformational ensembles in ion-mobility spectrometry and will help to predict and red-flag erroneous peaks in gas-phase based glycoanalysis. 1