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Charles M. Thompson
Professor

Phone: (406) 243-4643

Email: charles.thompson@umontana.edu

After completing undergraduate studies in chemistry at Rutgers University in New Jersey, Professor Thompson earned a M.S. and Ph.D. under the auspices of Professor T. Roy Fukuto at the University of California, Riverside. He also conducted post-doctoral training under the supervision of Professor E.J. Corey at Harvard University in 1982, and also with Professor Henry Rapoport at the University of California at Berkeley from 1983-1985. Professor Thompson is a medicinal and bioorganic chemist with interests in biologically active compounds.

Visit Dr. Thompson's Web Site

RESEARCH STATEMENT

Summary of Research Interests

General Interests:

Medicinal and bioorganic chemistry, synthesis and investigation of novel probes of enzyme structure and function, protein mass spectrometry & proteomics, enzyme inhibition and binding kinetics, pharmacophore development and computational modeling of proteins, immunoorganic chemistry.

  1. Glutamate Neurotransmitter System:
    We design and synthesize custom-tailored glutamate analogs to study and differentiate the pharmacology of the glutamate neurotransmitter system proteins, in particular, the excitatory amino acid transporters (EAAT) and glutamate vesicular transporter (VGLUT1). Research in our group also has focused on solving the proteome (the protein complement of the gene) complement of the neuronal vesicle. Using 2D electrophoresis and mass spectrometric fingerprinting techniques (trypsin digest), proteins in the vesicle system are identified via bioinformatics databases.

  2. Mechanism of Toxicity of Organophosphate Insecticides:
    We treated a neuroblastoma cell line (model system) with reactive and non-reactive OPs and are isolating and identifying OP-modified proteins using mass spectrometry. Since OPs modify acetylcholinesterase (AChE) at an essential serine, we selected an AChE active site sequence and chemically phosphorylated it at the catalytically important serine hydroxyl group. The native peptide sequence and phosphorylated sequence were used as haptens for antibody production. Our goal is to characterize and utilize polyclonal antibodies to differentiate between native and OP-modified AChE.

  3. Other Areas of Interest:
    a. Synthesis of phosphorus-containing analogs of alpha amino acids and their utility as inhibitors of matrix metalloproteinases.

    b. Synthesis and utility of novel protein probes (fluorescent, UV-Vis, spin label, etc.).
    For further research details see: http://www.umt.edu/medchem/curntres.htm
KEY PUBLICATIONS

PUBLICATIONS

Sá Santos, S.; Gibson, G.E.; Thompson, C.M.; Marques Alves, P.; Sonnewald, U. [U-13C]Glutamate and [1-13C]Glucose Metabolism are Impaired by Inhibitors of the a-Ketoglutarate Dehydrogenase Complex,  J. Neuroscience Res. 2006, 83, 450-458.

Spaulding, R.S.; George, K.M.; Thompson, C.M. Analysis and sequencing of the active site of acetylcholinesterase by electrospray ionization-quadrupole time-of-flight (QTOF) mass spectrometry. J. Chromatography B. 2006, 830, 105-113.

Thullbery, M.D.; Cox, H.D.; Schule, T.; Coughenour, H.D.; Thompson, C.M.; George, K.M. Differential Localization of Acetylcholinesterase in Neuronal and Non-neuronal Cells. J. Cell Biol. 2005, 170, 599-610.

Li, H; Schopfer, L.; Spaulding, R.; Thompson, C.M.; Lockridge, O. Identification of Organophosphate-Reactive Proteins by Tandem Mass Spectrometry. Chem-Biol Interact. 2005, 353–434, 157-158.

Peeples, E.; Schopfer, L.M.; Duysen, E.G.; Spaulding, R.; Voelker, T.; Thompson, C.M.; Lockridge, O.  Albumin, a New Biomarker of OP Exposure Identified by Mass Spectroscopy. Toxicological Sci. 2005 83, 303-312.

Lockridge, O., Duysen, E. G.; Voelker, T.; Thompson, C.M.; Schopfer, L.M. Life Without Acetylcholinesterase: The Implications of Cholinesterase Inhibitor Toxicity in AChE-Knockout Mice. Environ. Tox. Pharmacol. 2005, 19, 463-469.

Schopfer, L.M.; Voelker, T.; Bartels, C.F.; Thompson, C.M.; Lockridge, O.  Reaction Kinetics of Biotinylated Organophosphorus Toxicant, FP-biotin, with human acetylcholinesterase and human butyrylcholinesterase. Chem. Res. Toxicol. 2005 18, 747-754.

Thiagaraj, H.V.; Russo, E.B.; Burnett, A.; Goldstein, E.; Thompson, C.M.; Parker, K.K. Binding Properties of Dipropyltryptamine at the Human 5HT1a Receptor. Pharmacology 2005, 74, 193-199.

Thompson, C.M.; Coughenour, H.; Davis, E.; Carrigan, C.N.; Bridges, R.J. Gerdes, J.M. Inhibitors of Glutamate Vesicular Transport (VGLUT). Current. Med. Chem. 2005, 12 (18), 2041-2056.

Bunik, V. I.; Denton, T.T; Xu, H.; Thompson, C.M.; Cooper, A.J.L.; Gibson, G.E. Phosphonate Analogs of a-Ketoglutarate Inhibit the Activity of the a-Ketoglutarate Dehydrogenase Complex Isolated from Brain and in Cultured Cells. Biochemistry 2005, 44, 10552-10561.

Schopfer, L.M.; Champion, M.M.; Tamblyn, N.; Thompson, C.M.; Lockridge, O. Characteristic mass spectral fragments of the organophosphorus agent FP-biotin and FP-biotinylated peptides from trypsin and bovine albumin (Tyr410). Analytical. Biochem. 2005, 345, 121-132.

Coughenour, H.D.; Spaulding, R.S.; Thompson, C.M. The Synaptic Vesicle Proteome: A Comparative Study in Membrane Protein Identification. Proteomics 2004, 4, 3141-3155.

Thompson, C. M. and Richardson, R. J, In Pesticide Toxicology and International Regulation (Current Toxicology Series), Marrs, T. C. and Ballantyne, B. Anticholinesterase Insecticides. Eds. John Wiley & Sons Ltd, Chichester, 2004, 89-127.

Tongcharoensirikul, P.; Suarez, A.I.; Voelker, T. Thompson, C.M. Effect of Chiral Auxiliaries on the Stereoselective Addition of Dimethyl Thiophosphite to Imines. J. Org. Chem. 2004, 69, 2322-2326.

George, K.; Schule, T.; Sandoval, L.E.; Jennings, L.; Taylor, P.; Thompson, C.M. Differentiation between Acetylcholinesterase and the Organophosphate-inhibited Form Using Antibodies and the Correlation of Antibody Recognition with Reactivation Mechanism and Rate. J. Biol. Chem. 2003, 278, 45512 - 45518.

Doorn, J.A.; Thompson, C.M.; Christner, R.B.; Richardson, R.J. Stereoselective Inactivation of Torpedo Californica Acetylcholinesterase by Isomalathion: Inhibitory Reactions with (1R)- and (1S)-Isomers Proceed by Different Mechanisms. Chem. Res. Toxicol. 2003, 16, 958-965.

Trautmann, J.; Suarez, A.I.; Tongcharoensirikul, P.; Muth, G. W.; Thompson, C.M. A Facile Route to Substituted Phosphorothionates Using Dimethyl Phosphite. Phosphorus Sulfur Silicon Relat. Elem. 2002, 177, 471-477.

Carrigan, C.N.; Bartlett, R.D.; Esslinger, C.S.; Cybulski, K.A.; Tongcharoensirikul, P.; Bridges, R.J.; Thompson, C.M. Synthesis and in Vitro Pharmacology of Substituted Quinoline-2,4-Dicarboxylic Acids as Inhibitors of Glutamate Vesicular Transport (VGLUT), J. Med. Chem. 2002, 45, 2260-2276.

Denton, T.D.; Seib, T.; Bridges, R.J.; Thompson, C.M. Synthesis and Preliminary Biological Evaluation of trans-3,4-Conformationally-Restricted Glutamate and Pyroglutamate Analogs as Novel EAAT2 Inhibitors. Bioorg. Med. Chem.Lett. 2002 12, 3209-3213.

George, K. M.; Montgomery, M.A.; Sandoval, L.E.; Thompson, C.M. Examination of Cross-Antigenicity of Acetylcholinesterase and Butyrylcholinesterase using Anti-Acetylcholinesterase Antibodies. Tox. Letters. 2001, 126, 99-105.

Denton, T.T.; Thompson, C.M.; Cooper, A.J.L. Analysis of a-Ketoglutaric Acid Analogs as Substrates of Dehydrogenases and Transaminases. Analytical Biochem. 2001, 298, 265-274.