S. Bruce King

Education

BS, West Virginia University
MS, West Virginia University
PhD, Cornell University
Post-Doctoral, The Scripps Research Institute

Research Description

Our research program is based on a combination of organic chemistry, biochemistry, and biophysics directed towards understanding the various roles gasotransmitters, nitric oxide (NO), hydrogen sulfide (H₂S) and carbon monoxide (CO) and small molecules, hydrogen peroxide (H₂O₂ ), nitroxyl (HNO), nitrite (NO₂^– ) and nitrate (NO₃^– ) perform in biological systems. Nitric oxide, nitroxyl and hydrogen sulfide directly participate 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. These small molecules, especially NO also have been directly implicated in many areas of signaling with a relationship to cancer development/treatment. Our laboratory examines a number of specific areas of biological/medicinal chemistry in relation to these species:

1. The chemistry of the reactions of these small molecules with biological targets
   including co-factors
2. The abilitiy of nitroimidazole-based antibiotics, such as metronidazole and other neglected disease therapeutics, to release nitric oxide/nitroxyl and the role these reactive species play in the activity of these drugs
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, especially 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.

Publications

Holmila, R.J.; Vance, S.A.; King, S.B.; Tsang, A.W.; Singh, R.; Furdui, C.M.; “Silver Nanoparticles Induce Mitochondrial Protein Oxidation in Lung Cells Impacting Cell Cycle and Proliferation,” Antioxidants2019, 8, 552-567.  doi:10.3390/antiox8110552

Li, Z. Forshaw, T.E.; Holmila, R.J. Wu, H.; Poole, L.B.; Furdui, C.M.; King, S.B. “Triphenylphosphonium-Derived Protein Sulfenic Acid Trapping Agents: Synthesis, Reactivity and Effect on Mitochondrial Function,” Chem. Res. Toxicol. 2019, 32, 526-534, https://doi.org/10.1021/acs.chemrestox.8b00385

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.

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 PKGIα 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, https://doi.org/10.1021/acschembio.7b00444

Bolden, C.; King, S.B., Kim-Shapiro, D.B. “Reactions between nitrosopersulfide and heme proteins,” Free Radical Biology and Medicine, 2016, 90, 418-425, https://doi.org/10.1016/j.freeradbiomed.2016.09.005

Miao, Z., King, S.B. “Recent advances in the chemical biology of  nitrroxyl (HNO) detection and generation,” Nitric Oxide 2016, 57, 1-14, https://doi.org/10.1016/j.niox.2016.04.006

Miao, Z.; King, S.B. “Comparison of Reductive Ligation Strategies for Nitroxyl and S-Nitrosothiols,” ChemistryOpen, 2016, 5, 110-114, https://doi.org/10.1002/open.201500200

Awards and Accomplishments

MacDonough Family Faculty Fellowship, 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