LC/quadrupole ion trap mass spectroscopy system

说明(由申请人提供)：对于本提案中描述的九个由美国国立卫生研究院资助的核心项目的选择，所提议的液相色谱/四极杆离子陷阱(LC-ion trap MS-n)质谱学系统将提供重大改进。对于14名协查人员，拟议仪器的主要特点包括在全扫描模式下的高灵敏度/扫描速度、多阶段碎裂(ms-n)以及在自动扫描模式下的数据依赖采集。这些项目具有共同的需要，即需要识别药理制剂及其体内代谢物，以及它们在蛋白质水平上对细胞反应的影响。该仪器的主要用途将是利用我们正在开发的方法识别和表征生物基质中的低拷贝数蛋白质和多肽。我们建议的具体仪器是Thermo Finnigan LCQ Deca XP离子陷阱MS，它在纽约西部广阔的地理区域是独一无二的，并且将是唯一可供研究人员共享的同类仪器，他们需要直接接触该仪器，并需要更长的使用时间来开发新的蛋白质和多肽分析方法。它将被整合到现有的制药科学质谱学设施中，该设施由两台三重四极LC/MS-MS仪器组成。这一设施为从事基础、应用和临床生物医学研究以及分析质谱学的不同人群的研究人员提供了仪器。该设施利用率很高，在过去一个历年为调查人员提供了4000小时的现有LC/Triple Quad仪器的数据采集。质谱分析是NIH支持的许多项目的支柱，但该地区和大学缺乏Deca XP离子陷阱仪器将提供的补充能力。蛋白质组学和蛋白质化学分析项目因缺乏适合于鉴定和表征蛋白质和多肽的仪器而受到阻碍。此外，没有设施提供必要的扩展访问，以支持开发新的方法来定量低拷贝细胞蛋白转录本或具有治疗重要性的蛋白药物。拟议的仪器还将使小分子药物及其代谢物的识别和表征变得更加容易。鉴于我们的研究人员参与了具有高度临床相关性的研究，拟议的仪器将对威胁生命的疾病的新疗法的开发产生直接、重大的影响。

DESCRIPTION (provided by applicant): For the selection of nine core NIH-supported projects described in this proposal, the liquid chromatography/quadrupole ion trap (LC-ion trap MS-n) mass spectroscopy system proposed would provide major enhancement. For the 14 co-investigators, key features of the proposed instrument include high combined sensitivity/scan speed in full-scan mode, multi-stage fragmentation (Ms-n), and data-dependent acquisition in automated scan mode. The projects have in common the need for identification of pharmacological agents and their in vivo metabolites, as well as their effect on cellular responses at the protein level. A major use of the instrument will be the identification and characterization of low copy number proteins and peptides in biological matrices, using methods we are developing. The specific instrument we propose is the Thermo Finnigan LCQ Deca XP ion trap MS. It would be unique in the extended geographic region of Western New York, and would be the only instrument of its kind available on a shared basis for investigators who require the direct access to the instrument and the extended use time necessary to develop new analytical approaches for protein and peptide analysis. It will be integrated into the existing Pharmaceutical Sciences mass spectrometry facility, consisting of two triple quadrupole LC/MS-MS instruments. This facility provides instrument access to a diverse population of researchers engaged in basic, applied, and clinical biomedical research, as well as analytical mass spectrometry. The facility is highly utilized, providing investigators with 4,000 hours of data acquisition on the existing LC/triple quad instruments in the last calendar year. Mass spectrometric analysis is a mainstay of many NIH-supported projects, but this region and university lacks the complementary capabilities that the Deca XP ion trap instrument will provide. Proteomics and protein chemical analysis projects are hindered by the lack of an instrument well suited for identification and characterization of proteins and peptides. Furthermore, no facility exists to provide the extended access necessary to support the development of new methods for quantitation of low-copy cellular protein transcripts or therapeutically important protein drugs. The proposed instrumentation would also enable more facile identification and characterization of small-molecule drugs and their metabolites. Given the involvement of our investigators in studies of high clinical relevance, the proposed instrument would have direct, major impact on the development of new therapies for life-threatening diseases.