This Shared Instrumentation Grant application is for the purchase of an electrospray triple quadrupole mass spectrometer for the qualitative and quantitative analysis of peptides and other compounds of biomedical importance. The requested amount is based on the purchase of a VG Instruments Bio-Q instrument which presently represents the most economical system available with the required performance. It would be prudent, however, should this application be successful, to assess currently available instrumentation for electrospray triple quadrupole mass spectrometry at the time of funding. The proposed purchase would provide a significant extension to the mass spectrometry instrumentation (principally a hybrid tandem instrument equipped for fast atom bombardment ionization) presently employed and heavily committed in a number of research areas. Thus, the new instrument would (i) allow the establishment of additional collaborative programs not presently feasible because of pressure on a single instrument, and (ii) permit new applications of mass spectrometry by exploiting the unique properties of the recently devised electrospray procedure. Preliminary data obtained by the Program Director in collaboration with an existing user and one of the instrument manufacturers have established that superior sensitivities of detection may be achieved in the analyses of certain peptides (such as the vasoactive peptide, endothelin) using electrospray, thus establishing the feasibility of their trace analysis in biological extracts. In addition, the ability of the electrospray technique to achieve ionization of relatively large peptides opens new areas of application of mass spectrometry, for example in the characterization of xenobiotic/peptide conjugates. Furthermore, the typical generation of multiply charged ions by electrospray extends the mass range of analytes for which useful structural information may be obtained following collisional activation during tandem MS. Investigators who will share the new instrumentation and subjects of their research are as follows: K. Angelides (location and kinetics of peptide phosphorylation); R.G. Cook (confirmation of structure of synthetic peptides); S.J. Gaskell (characterization and quantification of peptide adducts, including leukotrienes and xenobiotic conjugates); H.F. Gilbert (characterization of peptide disulfide bridges); J. Moake/M. Phillips (characterization of polymeric aurin tricarboxylid acid, an inhibitor of von Willebrand Factor- mediated platelet aggregation); P.M. Vanhoutte (quantification of endothelin); C.-Y. Yang (characterization of modified apolipoprotein-B). Additionally and importantly, the Program Director is committed to a program of research to improve understanding of the analytical principles involved in these applications (such as the factors influencing the fragmentation of multiply charged ions).
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