Description of Research
Our research program is based on a combination of organic chemistry, biochemistry and biophysics directed towards understanding the various roles nitric oxide (NO) performs in biological systems. Nitroc 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. Recently our laboratory has focused on the some of the redox forms of nitric oxide, nitroxyl (HNO, one-electron reduced NO) and nitrite (NO2-, an oxidized nitrogen oxide), which have both generated interest based on their unique biological properties. Nitroxyl (HNO) remains a difficult molecule to study as it must be generated from precursors and it inherent reactivity makes identification relatively difficult. Specifically, we have pursued the synthesis and evaluation of new organic compounds as NO, HNO and nitrite delivery agents. As part of this study, we are attempting to better define the reactions of HNO with biological molecules (especially thiols) and develop new methods of detection. Other projects (with Dany Kim-Shapiro, WFU Physics) examine the development of organic molecules as sources of nitrite (shown to be an in vivo source of NO) as well as studying the fundamental reactions of this simple compound with biological compounds. Another major project (with Leslie Poole, WFU Biochemistry) attempts to define the sites, mechanisms and consequences of protein thiol oxidation (to sulfenic or sulfinic acids, S-nitrosothiols, or disulfides) through the synthesis of unique protein labels followed by mass spectroscopic studies of reactions with proteins and whole cells. Hopefully, these fundamental studies in chemical biology will provide a better idea of the process or redox chemistry in biology. --READ MORE--