LTQ-FT MS System for On-line Protein and Glycan Analysis

用于在线蛋白质和聚糖分析的 LTQ-FT MS 系统

• 批准号: 7498296
• 负责人: Catherine E. Costello
• 金额: $ 125.29万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7498296
• 关键词: Address; Affect; Aging; Amyloidosis; Basic Science; Bone Resorption; Boston; Carbohydrates; Cardiovascular Diseases; Cells; Clinical; Complex; Data; Degenerative Disorder; Disease; Dissociation; Drug Stability; Electrons; Electrospray Ionization; Eye; Funding; General Hospitals; Goals; Health; Human; Huntington Disease; Infectious Agent; Laboratories; Liquid Chromatography; Lyme Disease; Lymphoma; Mass Spectrum Analysis; Massachusetts; Minor; Modification; Online Systems; Osteogenesis; Performance; Phosphorylation; Polysaccharides; Post-Translational Protein Processing; Process; Proteins; Proteomics; Reflex action; Research Personnel; Research Project Grants; Resolution; Robotics; Sampling; Sickle Cell Anemia; System; Universities; Wound Healing; glycosylation; improved; instrument; instrumentation; leukemia; malignant breast neoplasm; mass spectrometer; meetings; nano; nitration; novel; protein structure; public health relevance

DESCRIPTION (provided by applicant): Within the Center for Biomedical Mass Spectrometry, the BUSM Mass Spectrometry Shared Instrumentation Laboratory operates two mass spectrometers (a Thermo-Fisher LTQ-Orbitrap and a Bruker Daltonics Reflex IV MALDI-TOF MS) dedicated to meeting the increasing and complex needs of NIH-funded investigators. We propose to purchase, install and operate a Thermo-Fisher 12-Tesla LC-LTQ FTMS system incorporating robotic sample handling, 1D and 2D nano-liquid chromatography, electrospray ionization, on-line Electron Capture Dissociation (ECD) and Infrared Multiphoton Dissociation (IRMPD), to provide data-dependent acquisition of high resolution-high mass accuracy spectra, increased sensitivity and reliable performance, with the goal to achieve high throughput, unambiguous identification and complete structural determinations of post-translationally modified proteins and structure elucidation of complex carbohydrates, to support the human health-related projects described in this proposal. MS and MSn spectra will be recorded online, with ECD and IRMPD dissociation and high mass accuracy being achieved in the ICR cell. The requested system will enable the Mass Spectrometry Shared Instrumentation Laboratory to implement functionality that does not exist at Boston University: that of on-line nanoLC- and high-throughput nanospray FTMS with ECD and IRMPD fragmentation. This capability will provide a group of NIH-funded investigators, whose projects are largely translational, with access to high sensitivity, high performance proteomics and glycomics analyses that focus on full characterization of post-translational modifications, including low-level phosphorylation, nitration, glycosylation and other structurally diverse and/or novel modifications which are keys to elucidating the mechanisms of complex diseases. Nine Major and four Minor research projects are proposed. All but one of these investigators are located on the BUSM campus; the other is located at Massachusetts General Hospital. PUBLIC HEALTH RELEVANCE The clinical and basic research of the Major Users includes bone resorption/ osteogenesis (Gerstenfeld), leukemia and breast cancer (Denis, Lerner), cardiovascular disease (Cohen), sickle cell disease (Steinberg), Lyme disease (Steere), infectious organisms (Samuelson and Robbins), wound healing in the eye (Trinkaus-Randall) and protein remodeling that accompanies aging and that affects drug stability (O'Connor). Projects of the Minor Users address lymphoma and breast cancer (Demierre, Seldin) and protein modifications that result in amyloid diseases and Huntington's Disease (Costello, Sherman). The proposed instrument system will accelerate progress towards understanding the mechanisms of these diseases and degenerative processes and will thus contribute directly toward improving human health.

描述（由申请人提供）：在生物医学质谱中心中，BUSM质谱法共享仪器实验室运营两个质谱仪（一个质谱仪LTQ-ORBITRAP和一个布鲁克Daltonics反射IV MALDI-TOF MS），该反射率是致力于满足NIHIH FUND型研究人员的日益增长和复杂需求。我们建议购买，安装和操作一个包括机器人样品处理，1D和2D纳米液体色谱，电喷雾电离，在线电子捕获分离（ECD）和提供数据依赖性量相关的群众群体相关性的群众群体相关性群体相关性群体相关性群体群体相关性群体相关性（IRMPD）的群体相关性（IRMPD），并提供了机器人样品处理，1D和2D Nano-liquid，电喷雾电离，在线电子捕获分离（ECD）和2D纳米 - 液体色谱，在线电子电离，在线电子捕获分离（ECD）和2D纳米 - 液态化，并提供了依赖数据依赖的群众，可靠的性能，目的是实现高通量，明确的识别和完整的翻译后修饰蛋白质的结构确定，并阐明复杂碳水化合物的结构，以支持本提案中与人类健康相关的项目。 MS和MSN光谱将在线记录，在ICR细胞中，ECD和IRMPD分离以及高质量精度。所请求的系统将使质谱共享的仪器实验室能够实施波士顿大学不存在的功能：在线纳米和高通量纳米喷雾nanospray ftms具有ECD和IRMPD碎片。 This capability will provide a group of NIH-funded investigators, whose projects are largely translational, with access to high sensitivity, high performance proteomics and glycomics analyses that focus on full characterization of post-translational modifications, including low-level phosphorylation, nitration, glycosylation and other structurally diverse and/or novel modifications which are keys to elucidating the mechanisms of complex疾病。提出了九个主要和四个次要的研究项目。这些调查人员中的所有人都位于Busm校园。另一个位于马萨诸塞州综合医院。 PUBLIC HEALTH RELEVANCE The clinical and basic research of the Major Users includes bone resorption/ osteogenesis (Gerstenfeld), leukemia and breast cancer (Denis, Lerner), cardiovascular disease (Cohen), sickle cell disease (Steinberg), Lyme disease (Steere), infectious organisms (Samuelson and Robbins), wound healing in the eye (Trinkaus-Randall) and protein伴随衰老并影响药物稳定性的重塑（O'Connor）。未成年人的项目解决淋巴瘤和乳腺癌（Demierre，Seldin）和蛋白质修饰，导致淀粉样蛋白疾病和亨廷顿氏病（Sherman Costello）。提出的仪器系统将加速进步，以了解这些疾病和退化过程的机制，从而直接有助于改善人类健康。

项目成果

Characterization of Isomeric Glycans by Reversed Phase Liquid Chromatography-Electronic Excitation Dissociation Tandem Mass Spectrometry.

通过反相液相色谱-电子激发解离串联质谱法表征异构聚糖。

• DOI: 10.1007/s13361-018-1943-9
• 发表时间: 2018
• 期刊: Journal of the American Society for Mass Spectrometry
• 影响因子: 3.2
• 作者: Tang,Yang;Wei,Juan;Costello,CatherineE;Lin,Cheng
• 通讯作者: Lin,Cheng

Gated Trapped Ion Mobility Spectrometry Coupled to Fourier Transform Ion Cyclotron Resonance Mass Spectrometry.

门控俘获离子淌度谱与傅里叶变换离子回旋共振质谱联用。

• DOI: 10.1007/s12127-016-0197-0
• 发表时间: 2016
• 期刊: International journal for ion mobility spectrometry : official publication of the International Society for Ion Mobility Spectrometry
• 作者: Ridgeway,MarkE;Wolff,JeremyJ;Silveira,JoshuaA;Lin,Cheng;Costello,CatherineE;Park,MelvinA
• 通讯作者: Park,MelvinA

Characterization and Quantification of Highly Sulfated Glycosaminoglycan Isomers by Gated-Trapped Ion Mobility Spectrometry Negative Electron Transfer Dissociation MS/MS.

通过门控离子迁移谱负电子转移解离 MS/MS 对高度硫酸化的糖胺聚糖异构体进行表征和定量。

• DOI: 10.1021/acs.analchem.8b05283
• 发表时间: 2019
• 期刊: Analytical chemistry
• 影响因子: 7.4
• 作者: Wei,Juan;Wu,Jiandong;Tang,Yang;Ridgeway,MarkE;Park,MelvinA;Costello,CatherineE;Zaia,Joseph;Lin,Cheng
• 通讯作者: Lin,Cheng

GAGrank: Software for Glycosaminoglycan Sequence Ranking Using a Bipartite Graph Model.

• DOI: 10.1016/j.mcpro.2021.100093
• 发表时间: 2021
• 期刊: Molecular & cellular proteomics : MCP
• 作者: Hogan JD;Wu J;Klein JA;Lin C;Carvalho L;Zaia J
• 通讯作者: Zaia J

Negative Electron Transfer Dissociation Sequencing of 3-O-Sulfation-Containing Heparan Sulfate Oligosaccharides.

含 3-O-硫酸化的硫酸乙酰肝素寡糖的负电子转移解离测序。

• DOI: 10.1007/s13361-018-1907-0
• 发表时间: 2018
• 期刊: Journal of the American Society for Mass Spectrometry
• 影响因子: 3.2
• 作者: Wu,Jiandong;Wei,Juan;Hogan,JohnD;Chopra,Pradeep;Joshi,Apoorva;Lu,Weigang;Klein,Joshua;Boons,Geert-Jan;Lin,Cheng;Zaia,Joseph
• 通讯作者: Zaia,Joseph