Jack Throck Watson
Emeritus Professor, Biochemistry
Emeritus Professor, Chemistry

• B.S., 1961, Iowa State University
• Ph.D., 1965, M.I.T.
• 1965-68, USAF School of Aerospace Medicine
• Postdoctoral Researcher, 1968-69; Institut de Chimie, Strasbourg, France
• 1969-1980, Faculty Member, Vanderbilt University
• 1988, 1995. Professeure Invité Ecole Normale Superieure, Paris. Analytical Chemistry

watsonj@msu.edu
501A Biochemistry Building
Michigan State University
East Lansing, MI 48824-1319
Office: 517-353-0855


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Jack Throck Watson

Research Interests

The major research theme in this laboratory involves the characterization of peptides and proteins by mass spectrometry with fast atom bombardment (FAB), electrospray ionization (ESI), and matrix assisted laser desorption ionization (MALDI). Unlike classical mass spectrometry involving electron ionization (EI), the desorption/ionization (D/I) techniques (FAB, ESI, and MALDI) provide little or no fragmentation, and thus no basis for deducing structural features in the molecule of interest. On the other hand, peptides and proteins are not amenable to analysis by EI because they have no significant vapor pressure, and thus must be analyzed by the DI techniques which yield only an indication of the molecular weight.

We develop and apply microchemical modifications of the analyte that can be interweaved with molecular weight determinations by D/I at various stages of controlled degradation of the analyte in an effort to obtain structural information.

Primary Structure:

By installing a functional group (triphenylphosphonium) containing a fixed charge at the N-terminus of a peptide, we can reliably generate a series of ions that facilitates recognition of the sequence of amino acids in peptides up to 15-20 residues. This procedure allows us to improve the success rate in sequencing peptides by FAB in conjunction with CAD-MS/MS, ESI with in-source fragmentation, or MALDI using post-source decay analysis.

Secondary Structure:

Determination of the connectivity of disulfide bonds in a peptide or protein is essential for complete characterization. Classical approaches to disulfide bond mapping involve the use of proteases which require a cleavage site in between the cysteines, a constraint that becomes quite serious as the cysteines lie close to one another, and impossible if the cysteines are adjacent in the sequence. Furthermore, the proteolytic approach frequently requires alkaline conditions under which disulfide bond exchange can occur during the digestion leading to likely artifact formation. MORE

Protein Folding:

Studies of the refolding pathways of an unfolded denatured protein are not only of academic interest, but of practical value in the pharmaceutical preparation oligopeptides formed via recombinant techniques. MORE

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