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Ned A. Porter

Title and Contact Information

Research 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 L, Porter NA. Reactivities and Products of Free Radical Oxidation of Cholestadienols. Journal of The American Chemical Society. 2014, 0(0): 0.[Epub ahead of print]

Codreanu SG, Ullery JC, Zhu J, Tallman KA, Beavers WN, Porter NA, Marnett LJ, Zhang B, Liebler DC. Alkylation Damage by Lipid Electrophile Targets functional Protein Systems. Molecular & Cellular. 2014, 0(0): 0.[Epub ahead of print]

Liu W, Xu L, Lamberson C, Haas D, Korade Z, Porter NA. A Highly Sensitive Method for Analysis of 7-dehydrocholesterol for the study of Smith-Lemli-Opitz Syndrome. The Journal of Lipid Research. 2014, 55(2): 329-337.

Lamberson CR, Xu L, Muchalski H, Montenegro-Burke JR, Shmanai VV, Bekish AV, McLean JA, Clarke CF, Shchepinov MS, Porter NA. Unusual Kinetic Isotope Effects of Deuterium Reinforced Polyunsaturated Fatty Acids in Tocopherol-Mediated Free Radical Chain Oxidations. Journal of The American Chemical Society. 2014, 136(3): 838-841.

Korade Z, Xu L, Harrison FE, Ahsen R, Hart SE,Folkes OM, Mirnics K, Porter NA. Antioxidant Supplementation Ameliorates Molecular Deficits in Smith-Lemli-Opitz Syndrome. Biological Psychiatry. 2014, 75(3): 215-222.

Shchepin RV, Liu W, Yin H, Zagol-Ikapitte I, Amin T, Jeong BS, Roberts LJ 2nd, Oates JA, Porter NA, Boutaud O. Rational Design of Novel Pyridinol-Fused Ring Acetaminophen Analogues. ACS Medicinal Chemistry Letters. 2013, 4(8): 710-714.

Windsor K, Genaro-Mattos TC, Kim HY, Liu W, Tallman KA, Miyamoto S, Korade Z, Porter NA. Probing lipid-protein adduction with alkynyl surrogates: application to Smith-Lemli-Opitz syndrome. The Journal of Lipid Research. 2013, 54(10): 2842-2850.

Korade Z, Xu L, Mirnics K, Porter NA. Lipid biomarkers of oxidative stress in a genetic mouse model of Smith-Lemli-Opitz syndrome. Journal of Inherited Metabolic Disease. 2013, 36(1): 113-122.

Liu W, Xu L, Lamberson CR, Merkens LS, Steiner RD, Elias ER, Haas D, Porter NA. Assays of Plasma Dehydrocholesteryl esters and Oxysterols from Smith-Lemli-Opitz syndrome patients. Journal of Lipid Research. 2013, 54(1): 244-253.

Tallman KA, Armstrong MD, Milne SB, Marnett LJ, Brown HA, Porter NA. Cobalt Carbonyl Complexes as Probes for Alkyne-Tagged Lipids. Journal of Lipid Research. 2013, 54(3): 859-868.

Xu L, Korade Z, Rosado DA Jr, Mirnics K, Porter NA. Metabolism of oxysterols derived from non-enzymatic oxidation of 7-dehydrocholesterol in cells. Journal of Lipid Research. 2013, (36): 1135-1143.

Porter NA. A Perspective on Free Radical Autoxidation: The Physical Organic Chemistry of Polyunsaturated Fatty Acid and Sterol Peroxidation. Journal of Organic Chemistry. 2013, (78): 3511-3524.

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.

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