S. Bruce King
PhD., Cornell University
Post Doctoral, The Scripps Research Institute,
Office: Wake Downtown, Rm. 3812
Phone: (336) 702-1954
Description of Research
Our research program is based on a combination of organic chemistry, bio-chemistry, and biophysics directed towards understanding the various roles gasotransmitters, nitric oxide (NO), nitroxyl (HNO), hydrogen sulfide (H2S) and carbon monoxide (CO) perform in biological systems. Nitric oxide, nitroxyl and hydrogen sulfide directly participates in the control of blood flow and pressure, neurotransmission, and the immune response and the regulation of their levels represents a therapeutic strategy for disease states characterized by abnormal production of these small molecules. Our laboratory examines a number of areas of biological/medicinal chemistry in relation to these species: 1) the potential nitric oxide producing reactions of metformin and the design of new metformin analogs to better understand the biochemistry for the use of this compound as a Type II diabetes treatment, 2) the abilitiy of nitroimidazole-based antibiotics, such as metronidazole, to release nitric oxide/nitroxyl and the role these reactive species play the activity of these drugs and 3) the overall redox properties of sulfur-containing biomolecules. With relation to sulfur biochemistry, our laboratory works on designing and synthesizing compounds to measure the redox status of sulfur-containg proteins, espeicially the formation of protein sulfenic acids and the total synthesis and biological chemistry of non-glutathione redox buffer thiols found in various micro-organisms. Many of these projects are completed in collaboration with other groups in chemistry, physics and the medical school. Students in our group are exposed to organic synthesis, biochemistry, molecular biology, biophysics (especially spectroscopy) and bio-analytical chemistry.
Holmila, R.J.; Vance, S.A.; Chen, X.; Wu, H.; Shukla, K.; Bharadwaj, R.S.; Mims, J.; Wary, Z., Marrs, G.; Singh, R.; Molina, A.J.; Poole, L.B.; King, S.B.; Furdui, C.M. “Mitochondria-targeted Probes for Imaging Protein Sulfenation,” Scientific Reports, 2018, 8:6635, 24493-24507.
Westcott, M.M.; Clemens, E.A.; Holbrook, B.C.; King, S.B.; Alexander-Miller, M.A. “The Choice of Linker for Conjugating R848 to Inactivated Influenza Virus Determines the Stimulatory Capacity for Innate Immune Cells,” Vaccine, 2018, 36, 1174-1182.
Donzelli, S.; Goetz, M.; Schmidt, K.; Wolters, M.; Stathopoulou, K.; Diering, S.; Prysyazhna, O.; Polat, V.; Scotcher, J.; Dees, C.; Subramanian, H.; Butt, E.; Kamynia, A.; Schobesberger, S.; King, S.B.; de Wit, C.; Leichert, L.I.; Feil, R.; Eaton, P.; Cuello, F. “Oxidant Sensor in the cGMP-Binding Pocket of PKGIa Regulates Nitroxyl-Mediated Kinase Activity,” Scientific Reports, 2017, 7, 9938-9952.
Chen, X.; Wu, H.; Park, C.M.; Poole, T.H.; Keceli, G.; Devarie-Baez, N.O.; Tsang, A.W.; Lowther, W.T.; Poole, L.B.; King, S.B.; Xian, M.; Furdui, C.M. “Discovery of Heteroaromatic Sulfones as a New Class of Biologically Compatible Thiol-Selective Reagents,” ACS Chemical Biology, 2017, 12, 2201-2208
Bolden, C.; King, S.B., Kim-Shapiro, D.B. “Reactions between nitrosopersulfide and heme proteins,” Free Radical Biology and Medicine, 2016, 90, 418-425.
Holbrook, B.C.; Kim, J.R.; Blevins, L.K.; Jorgenson, M.J.; Kock, N.D.; D’Agostino, R.B.; Aycok, S.T.; Hadimani, M.B.; King, S.B.; Parks, G.D.; Alexander-Miller, M.A. “A Novel R848-Conjugated Inactivated Influenza Virus Vaccine is Effacious and Safe in a Neonate Non-Human Primate Model,” Journal of Immunology, 2016, 197, 555-564.
Miao, Z., King, S.B. “Recent advances in the chemical biology of nitrroxyl (HNO) detection and generation,” Nitric Oxide 2016, 57, 1-14.
Miao, Z.; King, S.B. “Comparison of Reductive Ligation Strategies for Nitroxyl and S-Nitrosothiols,” ChemistryOpen, 2016, 5, 110-114.
Awards & Accomplishments
MacDonough Family Faculty Fellowship, Wake Forest University
Z. Smith Reynolds Foundation Leave, Wake Forest University
Z. Smith Reynolds Foundation Fellow, Wake Forest University
Established Investigator of the American Heart Association
Wake Forest University Award for Excellence in Research
Henry Dreyfus Teacher-Scholar
NIH Post-doctoral Fellow, The Scripps Research Institute
NIH Pre-doctoral Fellow, Cornell University
Swiger Pre-doctoral Fellowship, West Virginia University