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.
