TuO-02 KEYNOTE


SOLVING BIOCHEMICAL PROBLEMS WITH MASS SPECTROMETRY

Gary Siuzdak

The Scripps Research Institute, La Jolla, CA 92037, USA


Our lab is applying mass spectrometry to small biomolecules and large supramolecular complexes. We have explored its utility to identify unknowns, study covalent and noncovalent interactions, and analyze complexes measuring in millions of Daltons. One study has focused on identifying unknowns in biological fluids and the changes associated with physical stimuli. Utilizing electrospray, electron ionization, fast atom bombardment and tandem mass analysis, we have taken a purely chemical approach to the study of physiological changes associated with sleep. We have also investigated macromolecular and supramolecular complexes by studying the interactions of catalytic antibodies and the analysis of viruses. The studies on catalytic antibodies have yeilded informative results based upon indirect evidence such as charge state distribution and changes in molecular weight. We have also studied noncovalent complexes by observing supramolecular complexes following mass analysis to directly demonstrate that native conformations are preserved through the analysis process.

References:

  1. Cravatt, Prospero-Garcia, Siuzdak, Gilula, Henriksen, Boger, & Lerner, Science, 1995,1506.
  2. Krebs, Siuzdak, Dyson, Stewart, & Benkovic, Biochemistry, 1995, 34, 720.
  3. Siuzdak, Krebs, Benkovic, & Dyson, JACS, 1994, 116, 7937.
  4. Lerner, Siuzdak, Prospero-Garcia, Henriksen, Boger, & Cravatt, PNAS, 1994, 9505.

Acknowledge: This work was supported by The Lucille P. Markey Charitable Trust and National Institutes of Health.