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内，BUSM 质谱共享仪器实验室运行两台质谱仪（Thermo-Fisher LTQ-Orbitrap 和 Bruker Daltonics Reflex IV MALDI-TOF MS），致力于满足 NIH 资助的研究人员日益增长和复杂的需求。我们建议购买、安装和操作 Thermo-Fisher 12-Tesla LC-LTQ FTMS 系统，该系统结合了机器人样品处理、1D 和 2D 纳米液相色谱、电喷雾电离、在线电子捕获解离 (ECD) 和红外多光子解离 (IRMPD)，以提供高分辨率、高质量精度光谱的数据依赖型采集、提高灵敏度和 可靠的性能，目标是实现翻译后修饰蛋白质的高通量、明确识别和完整结构测定以及复杂碳水化合物的结构阐明，以支持本提案中描述的与人类健康相关的项目。 MS 和 MSn 谱图将在线记录，并在 ICR 池中实现 ECD 和 IRMPD 解离以及高质量准确度。所请求的系统将使质谱共享仪器实验室能够实现波士顿大学不存在的功能：具有ECD和IRMPD碎片的在线nanoLC和高通量纳喷雾FTMS。这种能力将为一组由 NIH 资助的研究人员提供高灵敏度、高性能的蛋白质组学和糖组学分析，这些研究人员的项目主要是转化性的，重点关注翻译后修饰的全面表征，包括低水平磷酸化、硝化、糖基化和其他结构多样和/或新颖的修饰，这些修饰是阐明复杂机制的关键 疾病。提出了九个主要研究项目和四个次要研究项目。除一名调查员外，所有调查员均位于 BUSM 校园内；另一个位于马萨诸塞州总医院。公共健康相关性 主要用户的临床和基础研究包括骨吸收/成骨（Gerstenfeld）、白血病和乳腺癌（Denis、Lerner）、心血管疾病（Cohen）、镰状细胞病（Steinberg）、莱姆病（Steere）、传染性微生物（Samuelson 和 Robbins）、眼部伤口愈合（Trinkaus-Randall）和蛋白质 伴随衰老并影响药物稳定性的重塑（O'Connor）。次要用户的项目涉及淋巴瘤和乳腺癌（Demierre、Seldin）以及导致淀粉样蛋白疾病和亨廷顿病（Costello、Sherman）的蛋白质修饰。拟议的仪器系统将加速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

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

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