Professor
Ph.D., Harvard University, 1970
n.porter@vanderbilt.edu

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:

1. 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”.


2. 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.


3. 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.


4. 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.

Selected Publications

Tallman KA, Rector CL, Porter NA. Substituent Effects on Regioselectivity in the Autoxidation of Nonconjugated Dienes. Journal of the American Chemical Society. 2009, 131 (15): 5635-5641.

Yin HY, Cox BE, Liu W, Porter NA, Morrow JD, Milne GL. Identification of intact oxidation products of glycerophospholipids in vitro and in vivo using negative ion electrospray iontrap mass spectrometry. Journal of Mass Spectrometry. 2009, 44 (5): 672-680.

Vila A, Tallman KA, Jacobs AT, Liebler DC, Porter NA, Marnett LJ. Identification of protein targets of 4-hydroxynonenal using click chemistry for ex vivo biotinylation of azido and alkynyl derivatives. Chemical Research in Toxicology. 2008, 21 (2): 432-444.

Schneider C, Boeglin WE, Yin HY, Porter NA, Brash AR. Intermolecular peroxyl radical reactions during autoxidation of hydroxy and hydroperoxy arachidonic acids generate a novel series of epoxidized products. Chemical Research in Toxicology. 2008, 21 (4): 895-903.

Brooks JD, Milne GL, Yin HY, Sanchez SC, Porter NA, Morrow JD. Formation of highly reactive cyclopentenone isoprostane compounds (A(3)/J(3)-isoprostanes) in vivo from eicosapentaenoic acid. Journal of Biological Chemistry. 2008, 283 (18): 12043-12055.

Schneider C, Porter NA, Brash AR. Routes to 4-hydroxynonenal: Fundamental issues in the mechanisms of lipid peroxidation. Journal of Biological Chemistry. 2008, 283 (23): 15539-15543.

Szapacs ME, Kim HYH, Porter NA, Liebler DC. Identification of proteins adducted by lipid peroxidation products in plasma and modifications of apolipoprotein A1 with a novel biotinylated phospholipid probe. Journal of Proteome Research. 2008, 7 (10): 4237-4246.

Schneider C, Niisuke K, Boeglin WE, Voehler M, Stec DF, Porter NA, Brash AR. Enzymatic synthesis of a bicyclobutane fatty acid by a hemoprotein lipoxygenase fusion protein from the cyanobacterium Anabaena PCC 7120. The Proceedings of the National Academy of Sciences United States of America. 2007, 104: 18941-5.

Vila A, Tallman KA, Porter NA, Liebler DC, Marnett LJ. Proteomic analysis of azido-HNE adducted proteins in RKO cells. Chemical Research in Toxicology. 2007, 20 (12): 2010-2010.

Nam TG, Rector CL, Kim HY, Sonnen AFP, Meyer R, Nau WM, Atkinson J, Rintoul J, Pratt DA, Porter NA. Tetrahydro-1,8-naphthyridinol analogues of alpha-tocopherol as antioxidants in lipid membranes and low-density lipoproteins. Journal of the American Chemical Society. 2007, 129 (33): 10211-10219.

Yin HY, Brooks JD, Gao L, Porter NA, Morrow JD. Identification of novel autoxidation products of the omega-3 fatty acid eicosapentaenoic acid in vitro and in vivo. Journal of Biological Chemistry. 2007, 282 (41): 29890-29901.

Tallman KA, Kim HYH, Ji JX, Szapacs ME, Yin HY, McIntosh TJ, Liebler DC, Porter NA. Phospholipid-protein adducts of lipid peroxidation: Synthesis and study of new biotinylated phosphatidylcholines. Chemical Research in Toxicology. 2007, 20 (2): 227-234.

Schneider C, Pratt DA, Porter NA, Brash AR. Control of oxygenation in lipoxygenase and cyclooxygenase catalysis. Chemistry & Biology. 2007, 14 (5): 473-488.

Yin H, Chacon A, Porter NA, Yin HY, Masterson DS. Free radical-induced site-specific peptide cleavage in the gas phase: Low-energy collision-induced dissociation in ESI- and MALDI mass spectrometry. Journal of the American Society for Mass Spectrometry. 2007, 18 (5): 807-816.

Yin HY, Gao L, Tai HH, Murphey LJ, Porter NA, Morrow JD. Urinary prostaglandin F-2 alpha is generated from the isoprostane pathway and not the cyclooxygenase in humans. Journal of Biological Chemistry. 2007, 282 (1): 329-336.

Davies S, Mitchell D, Sheller J, Nnodu U, Porter N, Roberts LJ. Pomegranate juice induces a beneficial shift in the profile of products formed by the isoprostane pathway. Free Radical Biology And Medicine. 2006, 41: S20-S21.

Wijtmans M, Rosenthal SJ, Zwanenburg B, Porter NA. Visible light excitation of CdSe nanocrystals triggers the release of coumarin from cinnamate surface ligands. Journal of the American Chemical Society. 2006, 128 (35): 11720-11726.

Chacon A, Masterson DS, Yin HY, Liebler DC, Porter NA. N-terminal amino acid side-chain cleavage of chemically modified peptides in the gas phase: A mass spectrometry technique for N-terminus identification. Bioorganic & Medicinal Chemistry. 2006, 14 (18): 6213-6222.

Davis TA, Gao L , Yin HY, Morrow JD, Porter NA,. In vivo and in vitro lipid peroxidation of arachidonate esters: The effect of fish oil omega-3 lipids on product distribution. Journal of the American Chemical Society. 2006, 128 (46): 14897-14904.

Roschek B, Tallman KA, Rector CL, Gillmore JG, Pratt DA, Punta C, Porter NA. Peroxyl radical clocks. Journal of Organic Chemistry. 2006, 71 (9): 3527-3532.

Gao L, Yin HY, Milne GL, Porter NA, Morrow JD. Formation of F-ring isoprostane-like compounds (F-3-isoprostanes) in vivo from eicosapentaenoic acid. Journal of Biological Chemistry. 2006, 281 (20): 14092-14099.

Nam TG, Boutaud O, Prart DA, Oates JA, Porter NA. Mechanistic studies of COX inhibition by acetaminophen. Prostaglandins & Other Lipid Mediators. 2006, 79 (1-2): 155-155.

Furse, K.E.; Pratt, D. A.; Schneider, C.; Brash, A. R.; Porter, N. A.; Lybrand, T. P.,. Molecular Dynamics Simulations of Arachidonic Acid-Derived Pentadienyl Radical Intermediate Complexes with COX-1 and COX-2: Insights into Oxygenation Regio- and Stereoselectivity. Biochemistry. 2006, 45: 3206-3218.

Furse, K.E.; Pratt, D. A.; Porter, N. A.; Lybrand, T. P.,. Molecular Dynamics Simulations of Arachidonic Acid Complexes with COX-1 and COX-2: Insights into Equilibrium Behavior. Biochemistry. 2006, 45: 3189-3205.

Yin H, Porter N, Morrow JD. The origin of prostaglandin F-2 alpha in human urine. Clinical Pharmacology & Therapeutics. 2006, 79 (2): P38-P38.

Specialties

• VICB
• Organic Chemistry
• Bioorganic Chemistry
• Biochemistry

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