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The Coward Laboratory

Representative Research Publications

I.  Organofluorine and Organophosphorous Chemistry: Modulating the Formation and Collapse of Tetrahedral Intermediates in Enzyme Catalysis.

   A.   Synthesis of Fluoroamino Acids
1. Tsukamoto, T.; Coward, J. K.; McGuire, J. J. Fluoroamino Acid-containing
    Analogues of Folic Acid and Methotrexate. In Biomedical Frontiers of Fluorine
; I. Ojima; J. R. McCarthy and J. T. Welch, Ed.; American Chemical
    Society: Washington, D.C., 1996; pp 118–128.
2. Konas, D.W.; Coward, J.K. Synthesis of L-4,4-Difluoroglutamic Acid viz
    Electrophilic Difluorination of a Lactam.Org. Lett., 1999, 1, 2105–2107.
3. Konas, D.W.; Coward, J.K.Electrophilic Fluorination of Pyroglutamic Acid
    Derivatives: Application of Substrate-Dependent Reactivity and Diastereoselectivity
    to the Synthesis of Optically Active 4-Fluoro­glutamic Acids.J. Org. Chem., 2001,
    66, 8831–8842.
4. Konas, D.W.; Pankuch, J.J.; Coward, J.K. The Synthesis of (2S)-4,4-
    Difluoroglutamyl g-Peptides Based on Garner’s Aldehyde and Fluoro-Reformatsky
    Chemistry. Synthesis-Stuttgart, 2002, 2616-2626.

   B.   Folate Biochemistry and Pharmacology
1. McGuire, J. J.; Hart, B. P.; Haile, W. H.; Magee, K. J.; Rhee, M.; Bolanowska,
    W. E.; Russell, C.; Galivan, J.; Paul, B.; Coward, J. K. Biological Properties of
    Fluoroglutamate-Containing Analogs of Folates and Methotrexate with Altered
    Capacities to Form Poly g Biochem. Pharmacol. 1996, 52, 1295–1303.
2. Pankuch, J.J.; Coward, J.K.N-Me-pAB-Glu-g-Glu-Tyr2 An Internally Quenched
    Flurorogenic g -Glutamyl Hydrolase Substrate. Bioorg. Med. Chem. Lett., 2001,
, 1561–1564.

   C.   Synthesis of Phosphapeptide “Tetrahedral Mimics”
1. Chen, S.; Lin, C.-H.; Kwon, D. S.; Walsh, C. T.; Coward, J. K. Design, synthesis,
    and biochemical evaluation of phosphonate and phosphonamidate analogs of
    glutathionylspermidine as inhibitors of glutathionylspermidine synthetase/amidase from
    Escherichia coli.J. Med. Chem.,1997, 40, 3842–3850.
2. Chen, S.; Coward, J. K. Investigations on new strategies for the facile synthesis of
    polyfunctionalized phosphinates: Phosphinopeptide analogs of
    glutathionylspermidine.J. Org. Chem., 63, 502–509.
3. Valiaeva, N.; Bartley, D.; Konno, T.; Coward, J.K. Phosphinic Acid
    Pseudopeptides Analogous to Glutamyl-Synthesis and Coupling to Pteroyl Azides
    Leads to Potent Inhibitors of Folylpoly­ g -glutamate Synthetase. J. Org. Chem.,
    2001, 66, 5146–5154.

   D.    “Tetrahedral Mimic” Biochemistry
1. Lin, C.-H.; Chen, S.; Kwon, D. S.; Coward, J. K.; Walsh, C. T. Aldehyde and
    Phosphinate Analogs of Glutathione and Glutathionylspermidine: Potent, Selective
    Binding Inhibitors of the E. coli Bifunctional Glutathionylspermidine
    Synthetase/Amidase.Chem. Biol., 1997, 4, 859–866.
2. Tsukamoto, T.; Haile, W. H.; McGuire, J. J.; Coward, J. K. Mechanism-based
    Inhibition of Human Folylpolyglutamate Synthetase: Design, Synthesis, and
    Biochemical Characterization of a Phosphapeptide Mimic of the Tetrahedral
    Intermediate. Arch. Biochem. Biophys.,1998, 355, 109–118.
3. McGuire, J.J.; Haile, W.H.; Valiaeva, N.; Bartley, D.; Guo, J.; Coward, J.K.
    Potent Inhibition of Human Folylpolyglutamate Synthetase by a Phosphinic Acid
    Mimic of the Tetrahedral Reaction Intermediate. Biochem. Pharmacol. 2003, 65,

II. N-linked Glycoprotein Biosynthesis: Merging of Carbohydrate and Peptide Synthesis with Glycobiology

   A.   Synthesis of Oligosaccharyltransferase Inhibitors
1. Xu, T.; Werner, R. M.; Lee, K.-C.; Fettinger, J. C.; Davis, J. T.; Coward, J. K.
    Synthesis and evaluation of tripeptides containing asparagine analogs as potential
    substrates or inhibitors of oligosaccharyl-transferase.J. Org. Chem., 1998, 63,
2. Xu, T.; Khanna, H.; Coward, J. K. The design, synthesis, and initial evaluation of
    benzophenone-containing peptides as potential photoaffinity labels of
    oligosaccharyltransferase. Bioorg. Med. Chem.,1998, 6, 1821–1834.
3. Hartman, M.C.T.; Coward, J.K. Synthesis of 5-Fluoro, N-Acetylglucosamine
    Glycosides and Pyrophosphates via Epoxide Fluoridolysis: Versatile Reagents for the
    Study of Glycoconjugate Biochemistry. J. Amer. Chem. Soc., 2002, 124,

   B.   Enzyme-Catalyzed Peptide Glycosylation
1. Xu, T.; Coward, J.K. The synthesis and use of 13 C and 15N-labeled peptide
    substrates as mechanistic probes of oligosaccharyltransferase. Biochemistry, 1997,
    48, 14683–14689.
2. Reddy, A.; Gibbs, B. S.; Liu, Y.-L.; Coward, J. K.; Changchien, L.-M.; Maley, F.
    Glycosylation of Overlapping Sequons in Yeast External Invertase. Site Selectivity In
. Glycobiology 1999, 9,547–555.
3. Gibbs, B. S.; Coward, J. K. Dolichylpyrophosphate oligosaccharides: Large-scale
    isolation and evaluation as oligosaccharyltransferase substrates. Bioorg. Med.
,1999, 6, 1160–1166.
4. Srinivasan, A.J.; Coward, J.K. A Biotin Capture Assay for
    Oligosaccharyltransferase. Anal. Biochem. 2002, 306, 328-335.

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