RUI: Glycan Characterization and Quantitative Analysis via Free-Radical Induced Dissociation

RUI：通过自由基诱导解离进行聚糖表征和定量分析

• 批准号: 1709272
• 负责人: Jinshan Gao
• 金额: $ 27.9万
• 依托单位: Montclair State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1709272&HistoricalAwards=false
• 关键词: RUI; Glycan; Characterization; Quantitative; Analysis

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Prof. Jinshan Gao and his students at Montclair State University are pursuing research that seeks improved capabilities for glycan characterization and quantitation. Glycans (or polysaccharides) are complex biomolecules that play important roles in the biochemistry of living systems, despite their low abundance. Their qualitative and quantitative analysis can be important in identifying and distinguishing healthy and diseased cells. Dr. Gao's group is targeting new ways to derive glycan structural information using mass spectrometry, one of the most widely used and important tools of chemical analysis. They are devising ways to label glycan molecules with isotopic or other chemical "tags" to gain better insight into their fragmentation and to facilitate their quantitation. The work seeks both improved performance and better understanding of the methods. Impact on workforce development is enhanced by involvement of undergraduate students, including first-generation college students and members from under-represented groups; Montclair State University is a Hispanic-Serving Institution. Elements of the research are integrated into Dr. Gao's undergraduate courses, enabling students to become familiar with modern analytical techniques. The overarching goals of the research are to develop a novel free-radical approach for glycan characterization and quantitation, and to investigate glycan dissociation induced by free radicals. Combining the merits of free-radical chemistry and mass spectrometry requires 1) development of free-radical reagents for glycan characterization; 2) development of free-radical tags for glycan quantitation; and 3) synthesis of model glycans for investigation of glycan dissociation mechanisms. These tasks provide a range of synthesis opportunities for the students engaged in the research. The free-radical reagents are employed to generate systematic and predictable glycan dissociation, facilitating visualization of the glycan skeleton. Free-radical tags enable simultaneous glycan quantitation and characterization. Insights gained from the investigation of glycan dissociation should improve understanding of the potential broader utility of the free-radical dissociation approach. The work should advance understanding of the roles of glycans in health and disease, including tumor development and other glycosylation-related diseases, such as coronary heart disease and inflammatory bowel disease.

在化学系化学测量和成像项目的支持下，蒙特克莱尔州立大学的高金山教授和他的学生正在开展研究，寻求提高聚糖表征和定量的能力。 聚糖（或多糖）是复杂的生物分子，尽管其丰度较低，但在生命系统的生物化学中发挥着重要作用。 它们的定性和定量分析对于识别和区分健康细胞和患病细胞非常重要。 高博士的团队正在寻找利用质谱法获取聚糖结构信息的新方法，质谱法是化学分析中使用最广泛和最重要的工具之一。 他们正在设计用同位素或其他化学“标签”标记聚糖分子的方法，以更好地了解其碎片并促进其定量。 这项工作旨在提高性能并更好地理解这些方法。 通过本科生（包括第一代大学生和代表性不足群体成员）的参与，可以增强对劳动力发展的影响；蒙特克莱尔州立大学是一所为西班牙裔服务的机构。该研究的要素已融入高博士的本科课程中，使学生能够熟悉现代分析技术。该研究的总体目标是开发一种用于聚糖表征和定量的新型自由基方法，并研究自由基诱导的聚糖解离。结合自由基化学和质谱的优点需要：1）开发用于聚糖表征的自由基试剂； 2) 开发用于聚糖定量的自由基标签； 3) 合成模型聚糖以研究聚糖解离机制。这些任务为从事研究的学生提供了一系列综合机会。 自由基试剂用于产生系统且可预测的聚糖解离，促进聚糖骨架的可视化。自由基标签可同时进行聚糖定量和表征。从聚糖解离研究中获得的见解应该可以增进对自由基解离方法潜在更广泛用途的理解。这项工作应该增进对聚糖在健康和疾病中的作用的理解，包括肿瘤发展和其他糖基化相关疾病，例如冠心病和炎症性肠病。

项目成果

Development of Novel Free Radical Initiated Peptide Sequencing Reagent: Application to Identification and Characterization of Peptides by Mass Spectrometry

新型自由基引发肽测序试剂的开发：质谱法在肽鉴定和表征中的应用

• DOI: 10.1007/s13361-018-2114-8
• 发表时间: 2018-12-13
• 期刊: Journal of The American Society for Mass Spectrometry
• 影响因子: 3.2
• 作者: Kaylee Gaspar;Kimberly Fabijanczuk;Tara Otegui;JoseRivera Acosta;Jinshan Gao
• 通讯作者: Jinshan Gao

Free-Radical-Mediated Glycan Isomer Differentiation

自由基介导的聚糖异构体分化

• DOI: 10.1021/acs.analchem.0c02213
• 发表时间: 2020-09
• 期刊: Analytical chemistry
• 影响因子: 7.4
• 作者: Murtada, Rayan;Fabijanczuk, Kimberly;Gaspar, Kaylee;Dong, Xueming;Zeyad Alzarieni, Kawthar;Calix, Kimberly;Manriquez, Edgar;Bakestani, Rose Mery;Kenttämaa, Hilkka I.;Gao, Jinshan
• 通讯作者: Gao, Jinshan

Resin and Magnetic Nanoparticle-Based Free Radical Probes for Glycan Capture, Isolation, and Structural Characterization

用于聚糖捕获、分离和结构表征的基于树脂和磁性纳米颗粒的自由基探针

• DOI: 10.1021/acs.analchem.9b01303
• 发表时间: 2019-12-17
• 期刊: Analytical Chemistry
• 影响因子: 7.4
• 作者: Fabijanczuk K;Gaspar K;Desai N;Lee J;Thomas DA;Beauchamp JL;Gao J
• 通讯作者: Gao J