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Ned A. Porter

Title and Contact Information

Professor
Office: 7962 SC
Phone: (615) 343-2693
Email

Education

Ph.D., Harvard University, 1970

Specialties

VICB
Organic Chemistry
Medicinal Chemistry
Chemical Biology
Bioorganic Chemistry
Biochemistry

In the News

Reporter-VU investigators develop new tool for tracking lipids
Reporter-York named chair of Department of Biochemistry
Reporter-Neuronal clues to cholesterol-defect disorder
Research News @ Vanderbilt-Ned Porter receives physical organic chemistry award
C&EN-Ned Porter has been awarded the James Flack Norris Award for Physical Organic Chemistry

Porter

Research

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

Xu LB, Sheflin LG, Porter NA, Fliesler SJ.7-Dehydrocholesterol-derived oxysterols and retinal degeneration in a rat model of Smith-Lemli-Opitz syndrome. Biochimica ET Biophysica Acta-Molecular And Cell Biology of Lipids. 2012, 1821 (6): 877-883.

Hill S, Lamberson CR, Xu LB, To R, Tsui HS, Shmanai VV, Bekish AV, Awad AM, Marbois BN, Cantor CR, Porter NA, Clarke CF, Shchepinov MS. Small amounts of isotope-reinforced polyunsaturated fatty acids suppress lipid autoxidation. Free Radical Biology And Medicine. 2012, 53 (4): 893-906.

Moller MN, Hatch DM, Kim HYH, Porter NA. Superoxide Reaction with Tyrosyl Radicals Generates para-Hydroperoxy and para-Hydroxy Derivatives of Tyrosine. Journal of the American Chemical Society. 2012, 134 (40): 16773-16780.

Xu LB, Sheflin LG, Porter NA, Fliesler SJ. 7-Dehydrocholesterol-derived oxysterols and retinal degeneration in a rat model of Smith-Lemli-Opitz syndrome. Biochimica ET Biophysica Acta-Molecular And Cell Biology of Lipids. 2012, 1821 (6): 877-883.

Yang JH, Chaurand P, Norris JL, Porter NA, Caprioli RM. Activity-Based Probes Linked with Laser-Cleavable Mass Tags for Signal Amplification in Imaging Mass Spectrometry: Analysis of Serine Hydrolase Enzymes in Mammalian Tissue. Analytical Chemistry. 2012, 84 (8): 3689-3695.

Xu LB, Mirnics K, Bowman AB, Liu W, Da J, Porter NA, Korade Z. DHCEO accumulation is a critical mediator of pathophysiology in a Smith-Lemli-Opitz syndrome model. Neurobiology of Disease. 2012, 45 (3): 923-929.

Yin HY, Xu LB, Porter NA. Free Radical Lipid Peroxidation: Mechanisms and Analysis. Chemical Reviews. 2011, 111 (10): 5944-5972.

Xu LB, Liu W, Sheflin LG, Fliesler SJ, Porter NA. Novel oxysterols observed in tissues and fluids of AY9944-treated rats: a model for Smith-Lemli-Opitz syndrome. Journal of Lipid Research. 2011, 52 (10): 1810-1820.

McGrath CE, Tallman KA, Porter NA Marnett LJ. Biological activities of 7-dehydrocholesterol-derived oxysterols: implications for Smith-Lemli-Opitz syndrome. Chemical Research in Toxicology. 2011, 24, 357-70.

Liu W, Porter NA, Schneider C, Brash AR, and Yin H. Formation of 4-hydroxynonenal from cardiolipin oxidation: Intramolecular peroxyl radical addition and decomposition. Free Radical Biology Medical. 2011, 50, 166-78. 10.1016/j.freeradbiomed. 2010.10.709

Nam TG, Ku JM, Park HG, Porter NA and Jeong BS. New synthetic route to N-tocopherol derivatives: Synthesis of pyrrolopyridinol analogue of α-tocopherol from pyridoxine. Organic & Biomolecular Chemistry. 2011, 9, 1749-55.

Morgan AH, Hammond VJ, Morgan L, Tallman K, Garcia-Diaz YR, McGuigan C, Serpi M, Porter NA, Murphy RC and O'Donnell VB. Quantitative assays for esterified oxylipins generated by immune cells. Nature Protocols. 2010, 5, 1919-31.

Shchepin R, Moller M, Kim HY, Hatch D,  Bartesaghi S, Kalyanaraman B, Radi R and Porter NA.Tyrosine-Lipid Peroxide Adducts from Radical Termination:  Para-Coupling and Intramolecular Diels-Alder Cyclization. Journal of the American Chemical Society. 2010, 132,17490–17500, DOI: 10.1021/ja106503a

Serwa R, Nam TG, Valgimigli L, Culbertson S, Rector CL, Jeong BS, Pratt DA, and Porter NA.Preparation and Investigation of Vitamin B6-Derived Aminopyridinol Antioxidants. Chemistry A European Journal. 2010, 16 14106-14 DOI: 10.1002/chem.201001382.

Korade Z, Xu L, Shelton R, Porter NA.Biological activities of 7-dehydrocholesterol-derived oxysterols: implications for Smith-Lemli-Opitz syndrome. Journal of Lipid Research. 2010, 51 (11): 3259-3269.

Kim H, Tallman KA, Codreanu SG, Liebler DD,Porter NA. Identification of Plasma Protein Targets of 4-Hydroxynonenal and Their Sites of Modification Utilizing Click cycloaddition, Photocleavable Linkers, and Shotgun Proteomics. Chemical Research in Toxicology. 2010, 23 (1): 276-276.

Nakajima T, Davies SS, Matafonova E, Potet F, Amarnath V, Tallman KA, Serwa RA, Porter NA, Balser JR, Kupershmidt S, Roberts LJ. Selective gamma-ketoaldehyde scavengers protect Na(V)1.5 from oxidant-induced inactivation. Journal of Molecular and Cellular Cardiology. 2010, 48 (2): 352-359.

Milne SB, Tallman KA, Serwa R, Rouzer CA, Armstrong MD, Marnett LJ, Lukehart CM, Porter NA, Brown HA. Capture and release of alkyne-derivatized glycerophospholipids using cobalt chemistry. Nature Chemical Biology. 2010, 6 (3): 205-207.

Omata Y, Saito Y, Yoshida Y, Jeong BS, Serwa R, Nam TG, Porter NA, Niki E. Action of 6-amino-3-pyridinols as novel antioxidants against free radicals and oxidative stress in solution, plasma, and cultured cells. Free Radical Biology and Medicine. 2010, 48 (10): 1358-1365.

Liu W, Yin HY, Akazawa YO, Yoshida Y, Niki E, Porter NA. Ex Vivo Oxidation in Tissue and Plasma Assays of Hydroxyoctadecadienoates: Z,E/E,E Stereoisomer Ratios. Chemical Research in Toxicology. 2010, 23 (5): 986-995.

Yin H, Davis TA, Porter NA. Simultaneous Analysis of Multiple Lipid Oxidation Products In Vivo by Liquid Chromatographic-Mass Spectrometry (LC-MS). Methods Molecular Biology. 2010, 610: 375-86.

Milne SB, Tallman KA, Serwa R, Rouzer CA, Armstrong MB, Marnett LJ, Lukehart CM, Porter NA, Brown HA. Alkyne-Derivatized Glycerophospholipids and Their Dicobalthexacarbonyl Complexes: A Highly Sensitive Analytical Approach for Determining Cellular Lipid Changes . Nature Chemical Biology. 2010, 6: 205-207.

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