May Meeting Announcement, Delaware Valley Mass Spectrometry Discussion Group

Manufacturer's Night, includes dinner and corporate posters. Please RSVP.

• Topic: "Scaling Mass Spectrometric Plateaus: Taking Full Chemical Advantage of Nature's Isotopic Complexity"

• Speaker: Alan G. Marshall, Florida State University

• Date: Monday, May 8, 2000. 6:00 PM

• Time: 6:00 Buffet Dinner hosted by Bruker Daltonics
  7:00 Socializing/Vendors presentations
  7:30 Talk

• RSVP for the Dinner to Scott Van Bramer by May 2.
  1. svanbram@science.widener.edu
  2. 610/499-4516

• Place: Merck, West Point, 37 Auditorium

• Abstract: Mass resolution for electrosprayed biomacromolecules as a function of mass spectrometer resolving power increases in steps. First, one must resolve different charge states. No additional peaks appear until adducts are resolved, and again until isotopic peaks are resolved, and finally isotopic "fine structure" (i.e., different elemental compositions of same nominal mass). For FT-ICR MS, each plateau extends ~100X higher mass than for other mass analyzers.
  (a) Accurate mass measurement (sub-ppm) of well-isolated peaks yields a unique elemental composition for species up to ~300 Da in mass.
  (b) That upper mass limit can be tripled by stable isotopic enrichment.
  (c) Mass resolving power is proportional to ion charge, so tht charge reduction of electrosprayed ions is unnecessary and detrimental.
  (d) Complex mixtures are resolved without prior chromatographic or gel separation.

  FT-ICR MS of electrosprayed extra heavy crude oil resolves and identifies elemental compositions of several thousand heteroatomic species from a single mass spectrum. Separately, we have generated a list of isobaric peptide pairs differing in exact mass due to 1, 2, or 3 mutations or post-translational modifications. Although the number of such isobars is high (>500 for 2 mutations/modifications), many have the same mass difference (e.g., CH4 vs. O). Virtually all can be resolved by ESI FT-ICR MS for peptides of 1,000-2,500 Da. We also show that the number of carbons in a biomolecule may be determined from the nominal mass difference between molecules expressed from natural abundance (1% 13C) and enriched (99% 13C) media. Once the number of carbons is known, the number of possible elemental compositions at a given mass measurement accuracy drops dramatically. Combined with accurate-mass MS/MS, it becomes possible to establish a unique elemental compositions for a phospholipid of ~900 Da.

  We demonstrate experimentally the linear relation between ion charge and mass resolving power, for electrosprayed ions whose isotopic distributions are resolved to <1 Da. Thus, charge reduction becomes unnecessary and is in fact undesirable. As long as the targeted mass spectral peaks can be resolved, there is no need to reduce the number of peaks, and charge reduction actually degrades resolution.

  We demonstrate experimentally the resolution of complex mixtures, ranging from arson accelerants (petroleum distillates, with hundreds of volatile components) to protein tryptic digests.

  H/D exchange will be shown to provide a way to map the protein segments at the contact interface in binary and ternary protein complexes for which NMR and x-ray data is unavailable.

  Work supported by NSF (CHE-99-09502), NIH (GM-31683), Florida State U., and the National High Magnetic Field Lab in Tallahassee, FL.

• Bio: ALAN G. MARSHALL received his B.A. degree in Chemistry from Northwestern University in 1965 and Ph.D. in Physical Chemistry from Stanford University in 1970. He joined the Chemistry faculty at the University of British Columbia (Vancouver, Canada) in 1969, and moved to Ohio State University in 1980 as Professor of Chemistry and Biochemistry and Director of the Campus Chemical Instrument Center. In 1993, he moved to Florida State University, where he is Distinguished Research Professor of Chemistry and Director of the Ion Cyclotron Resonance Program (recently renewed by NSF at $5.76M as a national user facility). He is best known for his co-invention (with M. B. Comisarow) and continuing leading development of Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry, for which he was elected to the rank of Fellow in both the American Physical Society and the American Association for the Advancement of Science in 1989. His recent recognitions include two national awards from the American Chemical Society and awards from the Spectroscopy Society of Pittsburgh and the American Society for Mass Spectrometry. He edits two journals and is on the editorial boards of three others. He has published three books, three patents, 296 refereed journal articles, and presented 844 talks/posters at conferences, universities, government labs, and industry. Applications for his work include FT-ICR instrumentation development, environmental analysis (e.g., oil spills), and mapping the structures of biological macromolecules and their complexes (e.g., tumor suppressor proteins, which control biological cell division).

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