Development of Charge Transfer Dissociation Mass Spectrometry (CTD-MS) of Oligosaccharides

低聚糖电荷转移解离质谱 (CTD-MS) 的开发

• 批准号: 1710376
• 负责人: Glen Jackson
• 金额: $ 45万
• 依托单位: West Virginia University Research Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1710376&HistoricalAwards=false
• 关键词: Development; Charge; Transfer; Dissociation; Mass

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Glen Jackson and his group at West Virginia University are developing instruments for the characterization of oligosaccharides - complex sugar molecules critical to living systems. Specifically, Dr. Jackson is assessing and expanding the usefulness of mass spectrometry as a means of determining the structure of these complex biomolecules. The research benefits from collaboration and student exchanges with a research team at the French National Institute for Agricultural Research (INRA) in Nantes, France. The tools being developed help answer important questions about the structure and function of biological molecules including, but not limited to, oligosaccharides. The new instruments can address, for example, questions about how sugars are digested, the gelling properties of food-grade pectins, and cell recognition pathways in living systems. The project is also providing a mechanism to educate elementary school students through organization of activity stations at local science fairs.The Jackson group is developing two mass spectrometers, a 2D and a 3D ion trap, for charge transfer dissociation (CTD) of oligosaccharides. Initial efforts seek to improve fragmentation efficiency by incorporating additional ion optics in the reactant ion beam. This modification may also reduce reaction times, enabling CTD to be coupled with ultra-high performance liquid chromatographic separations of complex mixtures. Instrument variables such as reagent ion kinetic energy, flux, and electron affinity (through the choice of noble gas); CTD reaction time; and the trapping parameter (qz) are optimized to enhance fragmentation behavior. Key aims are the elucidation of general rules for fragmentation and identification of the best conditions with which to augment oligosaccharide characterization. Isolated fractions of well-characterized oligosaccharides are used to elucidate the effect of oligosaccharide properties on the extent and nature of fragmentation. Properties expected to influence glycosidic and cross-ring fragmentation mechanisms include: glycan sequence, inter-residue linkage position, branching point, charge state, adducting ions, and glycan modifications such as esterification, amination and sulfation. Additional studies investigate the efficacy of CTD towards other oxygenated oligomers, including polymers, PEGylated drugs, anionic surfactants and oligonucleotides. These combined studies demonstrate the strengths and weaknesses of CTD relative to existing technologies and help guide future research towards high-impact applications.

在化学系化学测量和成像计划的支持下，西弗吉尼亚大学的格伦·杰克逊教授和他的团队正在开发用于表征低聚糖的仪器--对生命系统至关重要的复杂糖分子。具体地说，杰克逊博士正在评估和扩大质谱仪作为确定这些复杂生物分子结构的一种手段的有用性。这项研究得益于与法国南特法国国家农业研究所(INRA)的一个研究团队的合作和学生交流。正在开发的工具有助于回答有关生物分子的结构和功能的重要问题，包括但不限于寡糖。例如，这些新仪器可以解决糖是如何消化的问题，食品级果胶的凝胶特性，以及生命系统中的细胞识别途径。该项目还提供了一种机制，通过在当地科学博览会上组织活动站来教育小学生。杰克逊团队正在开发两种质谱仪，一种是2D和3D离子陷阱，用于低聚糖的电荷转移解离(CTD)。最初的努力是通过在反应物离子束中加入额外的离子光学元件来提高碎裂效率。这一改进还可以缩短反应时间，使CTD能够与复杂混合物的超高性能液相色谱分离相结合。优化了仪器变量，如试剂离子动能、通量和电子亲和力(通过选择惰性气体)；CTD反应时间；以及捕获参数(QZ)，以增强破碎行为。主要目的是阐明裂解的一般规则和确定增强低聚糖特性的最佳条件。特征明确的低聚糖的分离部分被用来阐明低聚糖性质对碎裂程度和性质的影响。预计会影响糖苷和跨环裂解机制的性质包括：糖链序列、残基间连接位置、支化点、电荷状态、加成离子和糖链修饰，如酯化、胺化和硫酸盐化。其他研究调查CTD对其他含氧低聚物的有效性，包括聚合物、聚乙二醇化药物、阴离子表面活性剂和寡核苷酸。这些综合研究表明了CTD相对于现有技术的优势和劣势，并有助于指导未来的研究走向高影响应用。

项目成果

Structural Characterization of Natural and Synthetic Macrocycles Using Charge-Transfer Dissociation Mass Spectrometry

使用电荷转移解离质谱法表征天然和合成大环化合物的结构

• DOI: 10.1021/jasms.1c00369
• 发表时间: 2022
• 期刊: Journal of the American Society for Mass Spectrometry
• 影响因子: 3.2
• 作者: Edwards, Halle M.;Sasiene, Zachary J.;Mendis, Praneeth M.;Jackson, Glen P.
• 通讯作者: Jackson, Glen P.

Structural characterization of human milk oligosaccharides using ultrahigh performance liquid chromatography–helium charge transfer dissociation mass spectrometry

超高效液相色谱-氦电荷转移解离质谱法表征母乳寡糖的结构

• DOI: 10.1093/glycob/cwac010
• 发表时间: 2022
• 期刊: Glycobiology
• 影响因子: 4.3
• 作者: Mendis, Praneeth M;Jackson, Glen P
• 通讯作者: Jackson, Glen P

The influence of Na/H exchange on the charge transfer dissociation (CTD) spectra of mannuronic acid oligomers

• DOI: 10.1016/j.ijms.2021.116634
• 发表时间: 2021-05
• 期刊: International Journal of Mass Spectrometry
• 影响因子: 1.8
• 作者: Zachary J. Sasiene;Praneeth M. Mendis;D. Ropartz;H. Rogniaux;Glen P. Jackson

Quantitative assessment of six different reagent gases for charge transfer dissociation (CTD) of biological ions

• DOI: 10.1016/j.ijms.2021.116532
• 发表时间: 2021-02-04
• 期刊: INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
• 影响因子: 1.8
• 作者: Sasiene，Zachary J.;Mendis，Praneeth M.;Jackson，Glen P.
• 通讯作者: Jackson，Glen P.

Ultra-high-performance liquid chromatography charge transfer dissociation mass spectrometry (UHPLC-CTD-MS) as a tool for analyzing the structural heterogeneity in carrageenan oligosaccharides

• DOI: 10.1007/s00216-021-03396-3
• 发表时间: 2021-05
• 期刊: Analytical and Bioanalytical Chemistry
• 影响因子: 4.3
• 作者: Praneeth M. Mendis;Zachary J. Sasiene;D. Ropartz;H. Rogniaux;Glen P. Jackson