Acquisition of a High Resolution TOF Mass Spectrometer

描述(由申请人提供)：该提案寻求购买一台TOF质谱仪和一台高效液相色谱仪，用于对天然产品、有机金属化合物、核酸和非极性有机合成中间体等小分子进行准确的质量测定，这些小分子是由美国国立卫生研究院支持的加州大学圣地亚哥分校三个系的六个主要研究小组产生的。高效液相-飞行时间将用于确定从海洋细菌和无脊椎动物获得的新天然产品的组成和配方，表征基因工程聚酮合成酶复合体的酶催化反应，用修饰的碱和糖成分制备的核酸，用于形成新的碳-碳键的有机金属化合物，或用于简单的热力学稳定分子的转化，如CO2和NO2。LC组分的分离能力将允许测量中等复杂的分馏天然产品提取物的非常少量的组分，并对天然产品生物合成中的反应路径和中间体进行“实时”监测。仪器规格的选择是为了提供广泛的样品类型的电离，从非极性有机中间体到分子质量高达~2000的高电荷水溶性分子，以及相对分子质量较大但可在多用户环境中使用的小多肽。) 公共卫生相关性：药物分子的研究高度依赖于高分辨率质谱学来准确测量分子质量。拟议的文书将加快由60多名相关研究人员组成的集体小组在发现治疗海洋生物癌症和传染病的新疗法方面的研究，以及开发诊断学。

DESCRIPTION (provided by applicant): The proposal seeks acquisition of a TOF mass spectrometer coupled with an HPLC for accurate mass determination of small molecules such as natural products, organometallic compounds, nucleic acids and non-polar organic synthetic intermediates that are generated in the research groups of six major NIH-supported research groups at three departments of University of California, San Diego. The HPLC-TOF will be used for determination of composition and formulas of novel natural products obtained from marine bacteria and invertebrates, characterize enzyme-catalyzed reactions of genetically-engineered polyketide synthase complexes, nucleic acids prepared with modified base and sugar components, organometallic compounds for novel carbon-carbon bond formation or for transformations of simple thermodynamically stable molecules such as CO2 and NO2. The separations capability of the LC component will allow measurements of very minor components of moderately complex fractionated natural product extracts, and 'real-time' monitoring of reaction pathways and intermediates in the biosynthesis of natural products. The instrumental specifications have been chosen to provide ionization of a broad range of sample types, from nonpolar organic intermediates to highly-charged water-soluble molecules of molecular masses up to ~2000 and small polypeptides of larger MW yet be amenable to walk-up usage in a multi-user environment.) PUBLIC HEALTH RELEVANCE: Research on drug molecules is highly dependent upon high-resolution mass spectrometry for accurate measurement of the masses of molecules. The proposed instrument will expedite research in discovery of new therapies for cancer and infectious from marine organisms and development of diagnostics by a collective group over 60 associated researchers.