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     Chemistry; 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,     11, 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,     315-318. 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,     4767–4778. 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,     10036–10053.    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     Vitro. Glycobiology 1999, 9,547–555. 3. Gibbs, B. S.; Coward, J. K. Dolichylpyrophosphate oligosaccharides: Large-scale     isolation and evaluation as oligosaccharyltransferase substrates. Bioorg. Med.     Chem.,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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