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

跳跃糖：质子化聚糖的分子机制重排马特乌斯·马里安斯基抽象的碳水化合物是三类重要的生物聚合物之一，参与它们的多种功能是由高度多样性促进的。聚糖分子结构的位置和适应性，有效地构成质谱分析是糖分析方法的一个主要挑战。 (MS) 方法通常因聚糖重排而变得复杂，其中分子 lar 机制仍未确定。为了分析结构先决条件并确定分子机制 anism 支撑重新安排，我将设计简化的采样协议它能够筛选构象（在一种拓扑内）和结构（即密度泛函理论方法能够在不同的离子拓扑之间进行调整。连接聚糖序列和带电聚糖的 3 维结构，能够预测热力学稳定的重排产物并提出初步建议分子机制。接下来，采样方案将应用于一组寡糖，其中已经观察到遵循不同机制的聚糖重排。可以包括小Lewis A和Y抗原及其唾液酸化中的岩藻糖迁移形式，以及更大的二触角 N-聚糖，而且这些聚糖的结构空间。罐，包括替代差向异构体，将被探索以量化结构先决条件拟议的暂定反应机制将是与波士顿大学林博士合作进行串联 MS 实验测试医学院。该提案提出了从解释性角色到探索性角色的范式转变—— 描述聚糖的理论方法实际上是全面的理解。聚糖结构空间的研究将揭示多重构象的发生离子淌度谱测定中的系综，将有助于预测和警告错误基于气相的糖分析中的峰。 1