Core B: Analytical & Synthetic Chemistry Core

核心 B：分析

• 批准号: 10653040
• 负责人: Zeneng Wang
• 金额: $ 21.11万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10653040
• 关键词: Acetates; Analytical Chemistry; Animal Model; Animals; Betaine; Biochemical; Biological; Biological Assay; Butyrates; Carbon; Cardiometabolic Disease; Cardiovascular Diseases; Carnitine; Cellular biology; Chemicals; Choline; Clinic; Clinical; Cost Savings; Coupled; Data Analyses; Detection; Development; Education; Elements; Enzyme Inhibitor Drugs; Enzymes; Equipment; Gas Chromatography; Generations; Goals; Hand; High Pressure Liquid Chromatography; Institution; Isomerism; Isotope Labeling; Isotopes; Knowledge; Laboratories; Liquid Chromatography; Liquid substance; Lyase; Mass Spectrum Analysis; Measurement; Metabolic Diseases; Methods; Modernization; Molecular Biology; Multinuclear NMR; Nutrient; Pathway interactions; Pattern; Propionates; Protons; Research Design; Research Personnel; Resolution; Sampling; Services; Site; Source; Spectroscopy, Fourier Transform Infrared; Structure; Students; Study models; Succinates; Synthesis Chemistry; System; Techniques; Time; Tissues; Tracer; Training; Training and Education; Universities; Validation; Volatile Fatty Acids; Volatilization; Wait Time; analytical tool; assay development; candidate identification; chemical synthesis; design; detector; experience; experimental study; gut microbiota; in vivo; inhibitor; instrumentation; interest; investigator training; light scattering; metabolomics; method development; microbial; operation; programs; small molecule; stable isotope; success; suicide substrates; tandem mass spectrometry; tool; trimethyloxamine

Analytical and Chemical Synthesis Core (Core B): Abstract The overall goals of the Analytical and Chemical Synthesis Core are to provide a diverse suite of analytical and organic synthetic chemical services. The core will provide unique access to a large variety of mass spectrometry assays, assay development expertise, as well as chemical synthesis support services for compound identification, provision of synthetic microbial enzyme inhibitors, and synthesis of isotope labeled standards and precursor molecules. This core will provide multiple analytical services in support of all Projects in the PPG. Moreover, all Projects rely heavily on mass spectrometry as both an investigative/discovery tool, and as a workhorse for quantitative analyses of biological and clinical samples. Mass spectrometry support includes both targeted and untargeted mass spectrometry platforms using as interface either liquid chromatography (LC) or gas chromatography (GC) systems, depending on experiment and analyte requirements. Compound identification services include both high resolution mass spectrometry platform capabilities, as well as chemical isolation, and multinuclear NMR platforms. Following untargeted mass spectrometry analyses and candidate metabolite identification, quantitative stable isotope dilution tandem mass spectrometry assays will be developed for metabolites of interest to the Projects. If the candidates are not available in commercial form (unlabeled or isotope labeled), they will be chemically synthesized as needed by the synthetic support services provided by the core. The core also offers a broad suite of quantitative LC/MS/MS assays of panels of gut microbiota generated metabolites, and GC/MS analyses of volatile analytes relevant to gut microbiota studies (e.g. short chain fatty acids). Heavy isotope labeled precursor compounds for isotope tracer studies (both in culture and for provision to animals), and synthesis of newly developed gut microbial enzyme inhibitors (cutC mechanism based inhibitors) will also be provided in sufficient quantity by the chemical synthesis support services of the core for animal model studies. The Core will also assist all Projects and Cores in the PPG in obtaining material for analysis and verification of analyte identities in each Project. Finally, the core will serve as a training hub for PPG investigators and students, providing expertise in operation of analytical and various other chemical equipment, methods development, study design, and oversight in use and operation of analytical equipment.

分析和化学合成核心(核心B)：摘要 分析和化学合成核心的总体目标是提供一套多样化的 分析和有机合成化学服务。核心将提供独特的途径，以获得大量的 质谱学分析、分析开发专业知识以及化学合成支持服务 化合物鉴定、合成微生物酶抑制剂的提供和同位素标记的合成 标准品和前体分子。 这一核心将提供多种分析服务，以支持PPG的所有项目。此外，所有项目 严重依赖质谱学作为研究/发现工具，也是定量分析的主力 生物样品和临床样品的分析。质谱学支持包括定向和非定向 使用液相色谱(LC)或气相色谱(GC)作为界面的质谱仪平台 系统，取决于实验和分析物要求。复合身份识别服务包括这两项 高分辨率质谱学平台能力，以及化学分离和多核核磁共振 站台。在非靶向质谱分析和候选代谢物鉴定之后， 将建立稳定的稳定同位素稀释串联质谱分析方法 对这些项目感兴趣。如果不能以商业形式(未标记或同位素标记)获得候选， 它们将根据需要由核心提供的合成支助服务进行化学合成。其核心是 还提供一套广泛的肠道微生物区系代谢产物的LC/MS/MS定量分析方法， 以及与肠道微生物区系研究相关的挥发性分析物的GC/MS分析(例如短链脂肪酸)。重的 用于同位素示踪研究的同位素标记前体化合物(在培养中和提供给动物)， 而新开发的肠道微生物酶抑制剂(基于CutC机制的抑制剂)的合成也将 由动物模型核心的化学合成支持服务提供充足的数量 学习。核心还将协助PPG中的所有项目和核心获得材料以供分析和 验证每个项目中的分析物身份。最后，核心将作为PPG的培训中心 研究人员和学生，提供分析和各种其他化学设备的操作专业知识， 方法分析仪器的开发、研究设计、使用和操作中的监督。