S. Bruce King
PhD., Cornell University
Post Doctoral, The Scripps Research Institute,
K. Barry Sharpless
Henry Dreyfus Teacher Scholar Award (1999-2004)
Z. Smith Reynolds Foundation Fellow (2001-2004)
Office: Salem 15B
Phone: (336) 758-5774
Description of Research
Our research program is based on a combination of organic chemistry, bio-chemistry, and biophysics directed towards understanding the various roles nitric oxide (NO) performs in biological systems. Nitric oxide directly participates in the control of blood flow and pressure, neurotransmission, and the immune response and the regulation of NO levels represents a therapeutic strategy for disease states characterized by abnormal NO production. Our laboratory examines a number of areas of NO chemistry: 1) the nitric oxide producing reactions of hydroxyurea and the interaction of hydroxyurea with biological targets to understand the chemistry responsible for the use of this compound as a sickle cell disease treatment, 2) the interaction of small molecules with nitric oxide synthase (NOS), the enzyme responsible for biochemical NO production from L-arginine and 3) the synthesis and evaluation of new organic NO and nitroxyl (HNO) delivery agents. In addition to these projects, our laboratory works on two other projects: 1) synthesizing compounds to measure the redox status of sulfur containing proteins and 2) the development of new synthetic organic methodology for the preparation of biologically active compounds. Students in our group are exposed to organic synthesis, biochemistry, molecular biology, biophysics (especially spectroscopy) and bio-analytical chemistry.
Miller, G.D.; Marsh, A.P.; Dove, R.W.; Beavers, D.; Presley, T.; Helms, C.; Bechtold, E.; King, S.B.; Kim-Shapiro, D.B. “Plasma Nitrate and Nitrite are Increased by a High-Nitrate Supplement but not by High-Nitrate Foods in Older Adults,” Nutr. Res. 2012, 32, 160-168.
Flores-Santana, W.; Moody, T.; Chen, W.; Gorczynski, M.J.; Shoman, M.E.; Velazquez, C.; Thetford, A.; Mitchell, J. B.; Cherukuri, M. K.; King, S. B.; Wink, D. A. “Nitroxide Derivatives of Non-Steroidal Anti-Inflammatory Drugs Exert Anti-Inflammatory and Superoxide Dismutase Scavenging Properties in A459 Cells,” Brit. J. Pharmacol. 2012, 165, 1058-1067.
Ding, W.; Li, Z.; Shen, X.; Martin, J.; King, S.B.; Sivakumaran, V.; Paolocci, N.; Gao, W. D.; “Reversal of Isoflurane-Induced Depression of Myocardial Contraction by Nitroxyl via Myofilament Sensitization to Ca+2,” Pharmacology and Experimental Therapeutics 2011, 339, 825-831.
Bates, D. J. P.; Smiterman, P. K.; Townsend, A. J.; King, S.B.; Morrow, C. S. “Nitroalkene Fatty Acids Mediate Activation of Nrf2/ARE-Dependent and PPARg-Dependent Transcription by Distinct Signaling Pathways and with Significantly Different Potencies,” Biochemistry 2011, 50, 7765-7773.
Reisz, J. A.; Zink, C. N.; King, S. B. “Rapid and Selective Nitroxyl (HNO) Trapping by Phosphines: Kinetics and New Aqueous Ligations for HNO Detection and Quantitation,” J. Am. Chem. Soc. 2011, 133, 11675-11685.
Wani, R.; Qian, J.; Yin, L.M.; Bechtold, E.; King, S. B.; Poole, L. B.; Paek, E.; Tsang, A. W.; Furdui, C. M. “Isoform-specific Regulation of Akt by PDGF-induced Reactive Oxygen Species,” Proc. Natl Acad. Sci., USA, 2011, 108, 10550-10555.
Qian, J.; Klomsiri, C.; Wright, M.W.; King, S. B.; Tsang, A. W.; Poole, L. B.; Furdui, C. M.; “Simple Synthesis of 1, 3-cyclopentanedione derived probes for labeling sulfenic acid proteins,” Chemical Commun. 2011, 47, 9203-9205.
DuMond, J. F.; King, S. B. “The Chemistry of Nitroxyl-Releasing Compounds,” Antioxidants and Redox Signaling, 2011, 14, 1637-1648.
Huang, Z.; Velazquez, C. A.; Abdellatif, K. R. A.; Chowdhury, M. A.; Reisz, J. A.; DuMond, J. F.; King, S. B.; Knaus, E. E. “Ethanesulfohydroxamic Acid Ester Prodrugs of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Synthesis, Nitric Oxide and Nitroxyl Release, Cyclooxygenase Inhibition, Anti-Inflammatory and Ulcerogenicity Index Studies,” J. Med. Chem. 2011, 54, 1356-1364.
Shoman, M. E.; Dumond, J.F.; Isbell, T. S.; Crawford, J. H.; Brandon A.; Honovar, J.; Vitturi, D. A.; White, C. R.; Patel, R. P.; King, S. B. “Acyloxy Nitroso Compounds as Nitroxyl (HNO) Donors: Kinetics, Reactions with Thiols and Vasodilation Properties,” J. Med. Chem. 2011, 54, 1059-1070.
Presley, T. D.; Morgan, A. R.; Bechtold, E.; Clodfelter, W.; Dove, R. W.; Jennings, J. M.; Kraft, R. A.; King, S. B.; Laurienti, P. J.; Rejeski, W. J.; Burdette, J. H.; Kim-Shapiro, D. B.; Miller, G. D. “Acute Effect of High Nitrtate Diet on Brain Perfusion in Older Adults,” Nitric Oxide, 2011, 24, 34-42.
Klomsiri, C.; Nelson, K. J.; Bechtold, E.; Soito, L.; Johnson, L. C.; Lowther, W. T.; Ryu, S-E.; King, S. B.; Furdui, C. M.; Poole, L. B. “Use of Dimedone-Based Chemical Probes for Sulfenic Acid Detection: Evaluation of Conditions Affecting Probe Incorporation into Redox-Sensitive Proteins,” Methods in Enzymology 2010, 473, 77-94.
Reisz, J. A.; Bechtold, E.; King, S. B. “Oxidative Heme Protein-Mediated Nitroxyl (HNO) Generation,” Dalton Trans., 2010, 39, 5203-5212.
Bechtold, E.; Reisz, J. A.; Klomsiri, C.; Allen W. Tsang, A. W.;Marcus W. Wright, M. W.; Poole, L. B.; Furdui, C. M.; King, S. B. “Water-Soluble Triarylphosphines as Biomarkers for Protein S-Nitrosation,” ACS Chemical Biology, 2010, 5, 405-414.