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Hopping Sugars: molecular mechanism of protonatedglycans rearrangement

跳跃糖：质子化聚糖重排的分子机制

基本信息

批准号：
10436332
负责人：
Mateusz Ryszard Marianski
金额：
$ 15.6万
依托单位：
HUNTER COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10436332
关键词：
Antigens Biological Process Biopolymers Boston Carbohydrates Cell Communication Cells Charge Collaborations Disease Dwarfism Fertilization Fucose Gases Genetic Programming Genomics Hand Immune response Immune system Ions Laboratories Lead Lewis Blood-Group System Link Mass Spectrum Analysis Methods Modeling Molecular Molecular Conformation Molecular Structure Monosaccharides Oligosaccharides Organism Pattern Phase Play Polysaccharides Positioning Attribute Potential Energy Process Proteins Proteomics Protocols documentation Reaction Role Sampling Site Space Models Spectrometry Spectrum Analysis Structure Techniques Testing Thermodynamics Tweens Universities Work base conformer density design electronic structure experimental study glycosylation improved in silico intercellular communication ion mobility ionization medical schools migration molecular dynamics molecular modeling molecular recognition novel operation quantum chemistry sugar theories three dimensional structure tool virtual

项目摘要

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

啤酒花糖：聚糖质子化的分子机制重排马特乌斯·马里安斯基摘要碳水化合物是三大类重要的生物聚合物之一，一系列的生物过程。它们的多种功能都由一个高潜水员- 聚糖分子结构的多样性和适应性，这是糖分析方法的主要挑战。质谱分析 (MS)方法通常因聚糖重排而复杂化，更大机制仍未确定。为了分析结构的先决条件和确定分子机制，基于重新安排的原则，我将设计简化的采样方案这是能够筛选构象（在一个拓扑结构）和结构（被- 在变化的离子拓扑之间）空间。密度泛函理论方法能够连接聚糖序列和带电聚糖的三维结构，能够预测化学稳定的重排产物，并提出初步的分子机制接下来将采样方案应用于低聚糖组，已观察到遵循不同机制的聚糖重排。这是Gly- 可以包括小刘易斯A和Y抗原中的岩藻糖迁移及其唾液酸化形式和较大的双触角N-聚糖。此外，这些gly的结构空间- 罐，包括替代差向异构体，将被探索，以量化结构的先决条件，管理机制的网站。拟议的初步反应机制将是与波士顿大学的林博士合作，医学院该提案建议将模式从解释性角色转变为探索性角色- 描述聚糖的理论方法。实际上，全面了解聚糖结构空间的变化将揭示多种构象的发生，在离子迁移谱仪合奏，并将有助于预测和红色标记错误在基于气相的糖分析中的峰。 1