Ned A. Porter
Organic and Bioorganic Chemistry
Our research group has interests in the areas of mechanistic, synthetic and bio-organic chemistry. Most of our research has centered on free radical chemistry. Areas of interest to us include: the mechanisms of the free radical reactions of natural products, such as lipids and phospholipids with molecular oxygen (a process important in the degradation of fats and oils and implicated in vivo); mechanisms and utility of free radical reactions; and the control of chemical and biological processes by means of light.
These studies are underway in our labs:
- We are exploring the free radical chemistry of organic compounds and molecular oxygen. This process is important in commerce because most commercial products are exposed to molecular oxygen and free radical initiating events. Of interest to these studies are the biologically important compounds that react readily with molecular oxygen, particularly unsaturated and polyunsaturated lipids. We are studying the mechanisms of the free radical oxidation reactions of lipids, known as lipid peroxidation, and we are developing methods for measuring the rates of free radical chain oxidation reactions by means of "free radical clocks".
- We have established collaborative research projects with groups in the Biochemistry, Pharmacology and Clinical Pharmacology Departments at Vanderbilt. These collaborations are central to an NIEHS Program Project Grant on "Lipid Oxidation and Antioxidant Mechanisms". One of the themes of this research is the chemistry of electrophiles that are generated in the decomposition of peroxide natural products formed in lipid peroxidation. These electrophiles react with nucleic acids and proteins and adducts formed have properties that are altered from the naturally occurring nucleic acids and proteins. We are developing procedures to prepare naturally occurring electrophiles derived from free radical oxidation of phospholipids and cholesterol esters and we are studying the reactions of these electrophiles with peptides and proteins. Critical to this research is the development of new strategies for identification of lipid-protein adducts by proteomics mass spectrometry methods.
- Another theme of our collaborative research is to define the products of polyunsaturated lipid oxidation and determine the mechanisms by which these compounds contribute to human disease. The over-arching hypotheses that govern the research are that the balance of competing oxidation pathways for different lipid substrates governs adaptation to oxidative stress and oxidative injury by controlling the distribution of bioactive lipid oxidation products. Analytical methods that make extensive use of HPLC MS/MS are being developed to help in the identification of lipid peroxidation products.
- We are studying the reactions of free radicals in lipoproteins and we are examining the effects of antioxidants on these processes. Polyunsaturated fatty acids and esters are important lipid constituents in biological membranes and in circulating lipid storage proteins, i.e. endogenous levels of lipoproteins such as LDL and HDL correlate with the development and progression of cardiovascular disease and peroxidation of lipids in these lipoproteins has been related to the advancement of disease processes.