This is an application for funds to purchase a triple quadruple mass spectrometer capable of performing mass spectrometry/mass spectrometry (MS/MS) experiments vital to biomedical research projects underway at the University of Iowa. The requested instrument is equipped with a gas chromatograph (GC) and a thermospray/plasmaspray interface to a high performance liquid chromatograph (HPLC), a fast atom bombardment (FAB) ion source, dynamic FAB, and an extended (4000 amu) mass range. These feature provide a substantial number of important capabilities not currently available to researchers on campus, including MS/MS, GC/MS/MS, HPLC/MS, HPLC/MS/MS, and FAB/MS/MS. This proposed GC/HPLC/MS/MS instrument will be located at the University of Iowa High Resolution Mass Spectrometry (HRMS) Facility, which is modeled after BRS program requirements for a shared usage resource, and operated by a Ph.D.-level MS specialist. At least 25 research groups involved in a wide range of research projects utilize the high-resolution magnetic sector mass spectrometer currently housed in the HRMS Facility. Of these, eight of the major users are involved in a total of fourteen PHS- supported research projects, each of which require MS capabilities not provided by the existing instrumentation. The requested MS/MS system has been carefully selected to complement existing capabilities, and to fulfill the needs of this group of biomedical researchers. Projects involving detailed structure elucidation of natural products, biomolecules, and components of complex mixtures provide the strongest justification for investment in the proposed system. Research projects of this nature described in this proposal include: structural studies of antibiotics and antitumor agents from marine fungi; characterization of vinca alkaloid biotransformation products; sequence analysis of heparin-derived oligosaccharides; structure determination of modified hydroxyeicosatetraenoic acids (HETEs); studies of folding and stability of ribonuclease proteins; sequencing of newly isolated enzymes and N-terminally blocked, cyclic, and straight chain peptides structural studies of transient and unstable metabolic products; and characterization of intermediates formed in the preparation of antileukemic and tumor promoting terpenoids. Support enabling the purchase of the proposed instrument would significantly accelerate these biomedical research projects by providing access to important state-of-the-art MS techniques for structure determination which are currently unavailable at the University of Iowa.
