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Lawrence Marnett
Faculty Member
Last active: 2/22/2016


A major interest in the Marnett laboratory is the structure and function of cyclooxygenase-2 (COX-2). This enzyme catalyzes the committed step in the production of prostaglandins and is the molecular target for non-steroidal antiinflammatory drugs. Functional analysis of COX-2 by structure-guided mutagenesis has uncovered new strategies for synthesizing COX-2 inhibitors and has suggested new biological roles for the enzyme. Current work focuses on the generation of novel antiinflammatory drugs with additional pharmacological functions and on investigations of the chemistry and biology of COX-2-dependent oxygenation of the endocannabinoid, 2-arachidonylglycerol, to glyceryl prostaglandins.

Another major interest in the Marnett laboratory is the chemistry and biology of DNA damage by endogenously generated products of oxidative stress. Individual products of DNA damage are incorporated into viral genomes for in vivo mutagenesis experiments. Similar experiments are used to identify human DNA repair enzymes that remove specific forms of DNA damage.

A new area of interest in the laboratory is the investigation of protein targets of drugs and toxic compounds and the consequences of protein modification in modulating biological function.

A broad range of techniques are used by the Marnett group including chemical synthesis, enzymology, protein expression, site-directed mutagenesis, bioanalytical chemistry, mass spectrometry, in vivo mutagenesis, tissue culture, proteomics, and techniques of signal transduction.


The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Conservative Secondary Shell Substitution In Cyclooxygenase-2 Reduces Inhibition by Indomethacin Amides and Esters via Altered Enzyme Dynamics. Konkle ME, Blobaum AL, Moth CW, Prusakiewicz JJ, Xu S, Ghebreselasie K, Akingbade D, Jacobs AT, Rouzer CA, Lybrand TP, Marnett LJ (2016) Biochemistry 55(2): 348-59
    › Primary publication · 26704937 (PubMed) · PMC4721528 (PubMed Central)
  2. Nuclear Oxidation of a Major Peroxidation DNA Adduct, M1dG, in the Genome. Wauchope OR, Beavers WN, Galligan JJ, Mitchener MM, Kingsley PJ, Marnett LJ (2015) Chem Res Toxicol 28(12): 2334-42
    › Primary publication · 26469224 (PubMed) · PMC4993022 (PubMed Central)
  3. Multitargeting of selected prostanoid receptors provides agents with enhanced anti-inflammatory activity in macrophages. Wang JW, Woodward DF, Martos JL, Cornell CL, Carling RW, Kingsley PJ, Marnett LJ (2016) FASEB J 30(1): 394-404
    › Primary publication · 26420849 (PubMed)
  4. Competition and allostery govern substrate selectivity of cyclooxygenase-2. Mitchener MM, Hermanson DJ, Shockley EM, Brown HA, Lindsley CW, Reese J, Rouzer CA, Lopez CF, Marnett LJ (2015) Proc Natl Acad Sci U S A 112(40): 12366-71
    › Primary publication · 26392530 (PubMed) · PMC4603459 (PubMed Central)
  5. nido-Dicarbaborate Induces Potent and Selective Inhibition of Cyclooxygenase-2. Neumann W, Xu S, Sárosi MB, Scholz MS, Crews BC, Ghebreselasie K, Banerjee S, Marnett LJ, Hey-Hawkins E (2016) ChemMedChem 11(2): 175-8
    › Primary publication · 26088701 (PubMed) · PMC4900168 (PubMed Central)
  6. Aberrant over-expression of COX-1 intersects multiple pro-tumorigenic pathways in high-grade serous ovarian cancer. Wilson AJ, Fadare O, Beeghly-Fadiel A, Son DS, Liu Q, Zhao S, Saskowski J, Uddin MJ, Daniel C, Crews B, Lehmann BD, Pietenpol JA, Crispens MA, Marnett LJ, Khabele D (2015) Oncotarget 6(25): 21353-68
    › Primary publication · 25972361 (PubMed) · PMC4673270 (PubMed Central)
  7. Targeted imaging of cancer by fluorocoxib C, a near-infrared cyclooxygenase-2 probe. Uddin MJ, Crews BC, Ghebreselasie K, Daniel CK, Kingsley PJ, Xu S, Marnett LJ (2015) J Biomed Opt 20(5): 50502
    › Primary publication · 25970082 (PubMed) · PMC4430360 (PubMed Central)
  8. Applications of azo-based probes for imaging retinal hypoxia. Uddin MI, Evans SM, Craft JR, Marnett LJ, Uddin MJ, Jayagopal A (2015) ACS Med Chem Lett 6(4): 445-9
    › Primary publication · 25893047 (PubMed) · PMC4394343 (PubMed Central)
  9. Next-generation sequencing reveals the biological significance of the N(2),3-ethenoguanine lesion in vivo. Chang SC, Fedeles BI, Wu J, Delaney JC, Li D, Zhao L, Christov PP, Yau E, Singh V, Jost M, Drennan CL, Marnett LJ, Rizzo CJ, Levine SS, Guengerich FP, Essigmann JM (2015) Nucleic Acids Res 43(11): 5489-500
    › Primary publication · 25837992 (PubMed) · PMC4477646 (PubMed Central)
  10. Action at a distance: mutations of peripheral residues transform rapid reversible inhibitors to slow, tight binders of cyclooxygenase-2. Blobaum AL, Xu S, Rowlinson SW, Duggan KC, Banerjee S, Kudalkar SN, Birmingham WR, Ghebreselasie K, Marnett LJ (2015) J Biol Chem 290(20): 12793-803
    › Primary publication · 25825493 (PubMed) · PMC4432295 (PubMed Central)
  11. Detection of non-melanoma skin cancer by in vivo fluorescence imaging with fluorocoxib A. Ra H, González-González E, Uddin MJ, King BL, Lee A, Ali-Khan I, Marnett LJ, Tang JY, Contag CH (2015) Neoplasia 17(2): 201-7
    › Primary publication · 25748239 (PubMed) · PMC4351298 (PubMed Central)
  12. Site-specific, intramolecular cross-linking of Pin1 active site residues by the lipid electrophile 4-oxo-2-nonenal. Aluise CD, Camarillo JM, Shimozu Y, Galligan JJ, Rose KL, Tallman KA, Marnett LJ (2015) Chem Res Toxicol 28(4): 817-27
    › Primary publication · 25739016 (PubMed) · PMC4480626 (PubMed Central)
  13. 13-Methylarachidonic acid is a positive allosteric modulator of endocannabinoid oxygenation by cyclooxygenase. Kudalkar SN, Nikas SP, Kingsley PJ, Xu S, Galligan JJ, Rouzer CA, Banerjee S, Ji L, Eno MR, Makriyannis A, Marnett LJ (2015) J Biol Chem 290(12): 7897-909
    › Primary publication · 25648895 (PubMed) · PMC4367288 (PubMed Central)
  14. Oxicams, a class of nonsteroidal anti-inflammatory drugs and beyond. Xu S, Rouzer CA, Marnett LJ (2014) IUBMB Life 66(12): 803-11
    › Primary publication · 25537198 (PubMed)
  15. Genetic disruption of 2-arachidonoylglycerol synthesis reveals a key role for endocannabinoid signaling in anxiety modulation. Shonesy BC, Bluett RJ, Ramikie TS, Báldi R, Hermanson DJ, Kingsley PJ, Marnett LJ, Winder DG, Colbran RJ, Patel S (2014) Cell Rep 9(5): 1644-53
    › Primary publication · 25466252 (PubMed) · PMC4268380 (PubMed Central)
  16. Fluorescent probes of the apoptolidins and their utility in cellular localization studies. DeGuire SM, Earl DC, Du Y, Crews BA, Jacobs AT, Ustione A, Daniel C, Chong KM, Marnett LJ, Piston DW, Bachmann BO, Sulikowski GA (2015) Angew Chem Int Ed Engl 54(3): 961-4
    › Primary publication · 25430909 (PubMed) · PMC4293314 (PubMed Central)
  17. Design of Fluorine-Containing 3,4-Diarylfuran-2(5H)-ones as Selective COX-1 Inhibitors. Uddin MJ, Elleman AV, Ghebreselasie K, Daniel CK, Crews BC, Nance KD, Huda T, Marnett LJ (2014) ACS Med Chem Lett 5(11): 1254-8
    › Primary publication · 25408841 (PubMed) · PMC4233350 (PubMed Central)
  18. Conjugation of cisplatin analogues and cyclooxygenase inhibitors to overcome cisplatin resistance. Neumann W, Crews BC, Sárosi MB, Daniel CM, Ghebreselasie K, Scholz MS, Marnett LJ, Hey-Hawkins E (2015) ChemMedChem 10(1): 183-92
    › Primary publication · 25318459 (PubMed) · PMC4480879 (PubMed Central)
  19. Identification of the major prostaglandin glycerol ester hydrolase in human cancer cells. Manna JD, Wepy JA, Hsu KL, Chang JW, Cravatt BF, Marnett LJ (2014) J Biol Chem 289(49): 33741-53
    › Primary publication · 25301951 (PubMed) · PMC4256310 (PubMed Central)
  20. Protein modification by adenine propenal. Shuck SC, Wauchope OR, Rose KL, Kingsley PJ, Rouzer CA, Shell SM, Sugitani N, Chazin WJ, Zagol-Ikapitte I, Boutaud O, Oates JA, Galligan JJ, Beavers WN, Marnett LJ (2014) Chem Res Toxicol 27(10): 1732-42
    › Primary publication · 25211669 (PubMed) · PMC4203390 (PubMed Central)
  21. Mechanism of repair of acrolein- and malondialdehyde-derived exocyclic guanine adducts by the α-ketoglutarate/Fe(II) dioxygenase AlkB. Singh V, Fedeles BI, Li D, Delaney JC, Kozekov ID, Kozekova A, Marnett LJ, Rizzo CJ, Essigmann JM (2014) Chem Res Toxicol 27(9): 1619-31
    › Primary publication · 25157679 (PubMed) · PMC4164229 (PubMed Central)
  22. Stable histone adduction by 4-oxo-2-nonenal: a potential link between oxidative stress and epigenetics. Galligan JJ, Rose KL, Beavers WN, Hill S, Tallman KA, Tansey WP, Marnett LJ (2014) J Am Chem Soc 136(34): 11864-6
    › Primary publication · 25099620 (PubMed) · PMC4151707 (PubMed Central)
  23. Structure and Stereochemical Determination of Hypogeamicins from a Cave-Derived Actinomycete. Derewacz DK, McNees CR, Scalmani G, Covington CL, Shanmugam G, Marnett LJ, Polavarapu PL, Bachmann BO (2014) J Nat Prod 77(8): 1759-63
    › Primary publication · 25046128 (PubMed) · PMC4334282 (PubMed Central)
  24. ω-Alkynyl lipid surrogates for polyunsaturated fatty acids: free radical and enzymatic oxidations. Beavers WN, Serwa R, Shimozu Y, Tallman KA, Vaught M, Dalvie ED, Marnett LJ, Porter NA (2014) J Am Chem Soc 136(32): 11529-39
    › Primary publication · 25034362 (PubMed) · PMC4140476 (PubMed Central)
  25. Central anandamide deficiency predicts stress-induced anxiety: behavioral reversal through endocannabinoid augmentation. Bluett RJ, Gamble-George JC, Hermanson DJ, Hartley ND, Marnett LJ, Patel S (2014) Transl Psychiatry : e408
    › Primary publication · 25004388 (PubMed) · PMC4119220 (PubMed Central)
  26. Trifluoromethyl fluorocoxib a detects cyclooxygenase-2 expression in inflammatory tissues and human tumor xenografts. Uddin MJ, Crews BC, Huda I, Ghebreselasie K, Daniel CK, Marnett LJ (2014) ACS Med Chem Lett 5(4): 446-50
    › Primary publication · 24900856 (PubMed) · PMC4027729 (PubMed Central)
  27. Impact of structural and metabolic variations on the toxicity and carcinogenicity of hydroxy- and alkoxy-substituted allyl- and propenylbenzenes. Rietjens IM, Cohen SM, Fukushima S, Gooderham NJ, Hecht S, Marnett LJ, Smith RL, Adams TB, Bastaki M, Harman CG, Taylor SV (2014) Chem Res Toxicol 27(7): 1092-103
    › Primary publication · 24857813 (PubMed)
  28. Substrate-selective COX-2 inhibition as a novel strategy for therapeutic endocannabinoid augmentation. Hermanson DJ, Gamble-George JC, Marnett LJ, Patel S (2014) Trends Pharmacol Sci 35(7): 358-67
    › Primary publication · 24845457 (PubMed) · PMC4074568 (PubMed Central)
  29. PET radiotracer [¹⁸F]-P6 selectively targeting COX-1 as a novel biomarker in ovarian cancer: preliminary investigation. Perrone MG, Malerba P, Uddin MJ, Vitale P, Panella A, Crews BC, Daniel CK, Ghebreselasie K, Nickels M, Tantawy MN, Manning HC, Marnett LJ, Scilimati A (2014) Eur J Med Chem : 562-8
    › Primary publication · 24832612 (PubMed) · PMC4401082 (PubMed Central)
  30. Conjugates of cisplatin and cyclooxygenase inhibitors as potent antitumor agents overcoming cisplatin resistance. Neumann W, Crews BC, Marnett LJ, Hey-Hawkins E (2014) ChemMedChem 9(6): 1150-3
    › Primary publication · 24801194 (PubMed) · PMC4136547 (PubMed Central)
  31. GRASr2 evaluation of aliphatic acyclic and alicyclic terpenoid tertiary alcohols and structurally related substances used as flavoring ingredients. Marnett LJ, Cohen SM, Fukushima S, Gooderham NJ, Hecht SS, Rietjens IM, Smith RL, Adams TB, Bastaki M, Harman CL, McGowen MM, Taylor SV (2014) J Food Sci 79(4): R428-41
    › Primary publication · 24689743 (PubMed)
  32. Alkylation damage by lipid electrophiles targets functional protein systems. Codreanu SG, Ullery JC, Zhu J, Tallman KA, Beavers WN, Porter NA, Marnett LJ, Zhang B, Liebler DC (2014) Mol Cell Proteomics 13(3): 849-59
    › Primary publication · 24429493 (PubMed) · PMC3945913 (PubMed Central)
  33. Oxicams bind in a novel mode to the cyclooxygenase active site via a two-water-mediated H-bonding Network. Xu S, Hermanson DJ, Banerjee S, Ghebreselasie K, Clayton GM, Garavito RM, Marnett LJ (2014) J Biol Chem 289(10): 6799-808
    › Primary publication · 24425867 (PubMed) · PMC3945341 (PubMed Central)
  34. Mass spectrometric methods for the analysis of nucleoside-protein cross-links: application to oxopropenyl-deoxyadenosine. Shuck SC, Rose KL, Marnett LJ (2014) Chem Res Toxicol 27(1): 136-46
    › Primary publication · 24359270 (PubMed) · PMC3925670 (PubMed Central)
  35. Cytotoxicity of 1,4-diamino-2-butanone, a putrescine analogue, to RKO cells: mechanism and redox imbalance. Soares CO, Boiani M, Marnett LJ, Bechara EJ (2013) Free Radic Res 47(9): 672-82
    › Primary publication · 23758064 (PubMed)
  36. The 2'-Trifluoromethyl Analogue of Indomethacin Is a Potent and Selective COX-2 Inhibitor. Blobaum AL, Uddin MJ, Felts AS, Crews BC, Rouzer CA, Marnett LJ (2013) ACS Med Chem Lett 4(5): 486-490
    › Primary publication · 23687559 (PubMed) · PMC3654564 (PubMed Central)
  37. Molecular imaging of cyclooxygenase-2 in canine transitional cell carcinomas in vitro and in vivo. Cekanova M, Uddin MJ, Bartges JW, Callens A, Legendre AM, Rathore K, Wright L, Carter A, Marnett LJ (2013) Cancer Prev Res (Phila) 6(5): 466-76
    › Primary publication · 23531445 (PubMed) · PMC3671760 (PubMed Central)
  38. Targeted protein capture for analysis of electrophile-protein adducts. Connor RE, Codreanu SG, Marnett LJ, Liebler DC (2013) Methods Mol Biol : 163-76
    › Primary publication · 23475677 (PubMed) · PMC3801415 (PubMed Central)
  39. Advancing the translation of optical imaging agents for clinical imaging. Sevick-Muraca EM, Akers WJ, Joshi BP, Luker GD, Cutler CS, Marnett LJ, Contag CH, Wang TD, Azhdarinia A (2013) Biomed Opt Express 4(1): 160-70
    › Primary publication · 23304655 (PubMed) · PMC3539189 (PubMed Central)
  40. 2-Carbaborane-3-phenyl-1H-indoles--synthesis via McMurry reaction and cyclooxygenase (COX) inhibition activity. Laube M, Neumann W, Scholz M, Lönnecke P, Crews B, Marnett LJ, Pietzsch J, Kniess T, Hey-Hawkins E (2013) ChemMedChem 8(2): 329-35
    › Primary publication · 23303738 (PubMed) · PMC3849512 (PubMed Central)
  41. Cannabinoid receptor 1 suppresses transient receptor potential vanilloid 1-induced inflammatory responses to corneal injury. Yang Y, Yang H, Wang Z, Varadaraj K, Kumari SS, Mergler S, Okada Y, Saika S, Kingsley PJ, Marnett LJ, Reinach PS (2013) Cell Signal 25(2): 501-11
    › Primary publication · 23142606 (PubMed) · PMC3607947 (PubMed Central)
  42. Single-dose safety and pharmacokinetic evaluation of fluorocoxib A: pilot study of novel cyclooxygenase-2-targeted optical imaging agent in a canine model. Cekanova M, Uddin MJ, Legendre AM, Galyon G, Bartges JW, Callens A, Martin-Jimenez T, Marnett LJ (2012) J Biomed Opt 17(11): 116002
    › Primary publication · 23117797 (PubMed) · PMC3484194 (PubMed Central)
  43. Measuring electrophile stress. Tallman KA, Vila A, Porter NA, Marnett LJ (2009) Curr Protoc Toxicol : Unit17.11
    › Primary publication · 23045010 (PubMed)
  44. Translesion synthesis across 1,N6-(2-hydroxy-3-hydroxymethylpropan-1,3-diyl)-2'-deoxyadenosine (1,N6-γ-HMHP-dA) adducts by human and archebacterial DNA polymerases. Kotapati S, Maddukuri L, Wickramaratne S, Seneviratne U, Goggin M, Pence MG, Villalta P, Guengerich FP, Marnett L, Tretyakova N (2012) J Biol Chem 287(46): 38800-11
    › Primary publication · 22977231 (PubMed) · PMC3493922 (PubMed Central)
  45. Crystal structure of 12-lipoxygenase catalytic-domain-inhibitor complex identifies a substrate-binding channel for catalysis. Xu S, Mueser TC, Marnett LJ, Funk MO (2012) Structure 20(9): 1490-7
    › Primary publication · 22795085 (PubMed)
  46. Ortho-carbaborane derivatives of indomethacin as cyclooxygenase (COX)-2 selective inhibitors. Scholz M, Blobaum AL, Marnett LJ, Hey-Hawkins E (2012) Bioorg Med Chem 20(15): 4830-7
    › Primary publication · 22748709 (PubMed) · PMC3408963 (PubMed Central)
  47. Identifying mechanism-of-action targets for drugs and probes. Gregori-Puigjané E, Setola V, Hert J, Crews BA, Irwin JJ, Lounkine E, Marnett L, Roth BL, Shoichet BK (2012) Proc Natl Acad Sci U S A 109(28): 11178-83
    › Primary publication · 22711801 (PubMed) · PMC3396511 (PubMed Central)
  48. Seeing it through: translational validation of new medical imaging modalities. Aldrich MB, Marshall MV, Sevick-Muraca EM, Lanza G, Kotyk J, Culver J, Wang LV, Uddin J, Crews BC, Marnett LJ, Liao JC, Contag C, Crawford JM, Wang K, Reisdorph B, Appelman H, Turgeon DK, Meyer C, Wang T (2012) Biomed Opt Express 3(4): 764-76
    › Primary publication · 22574264 (PubMed) · PMC3345805 (PubMed Central)
  49. Protein modification by oxidized phospholipids and hydrolytically released lipid electrophiles: Investigating cellular responses. Ullery JC, Marnett LJ (2012) Biochim Biophys Acta 1818(10): 2424-35
    › Primary publication · 22562025 (PubMed) · PMC3398744 (PubMed Central)
  50. Inflammation and cancer: chemical approaches to mechanisms, imaging, and treatment. Marnett LJ (2012) J Org Chem 77(12): 5224-38
    › Primary publication · 22515568 (PubMed) · PMC3375764 (PubMed Central)
  51. Arrest of human mitochondrial RNA polymerase transcription by the biological aldehyde adduct of DNA, M1dG. Cline SD, Lodeiro MF, Marnett LJ, Cameron CE, Arnold JJ (2010) Nucleic Acids Res 38(21): 7546-57
    › Primary publication · 20671026 (PubMed) · PMC2995074 (PubMed Central)
  52. Characterization of an AM404 analogue, N-(3-hydroxyphenyl)arachidonoylamide, as a substrate and inactivator of prostaglandin endoperoxide synthase. Turman MV, Kingsley PJ, Marnett LJ (2009) Biochemistry 48(51): 12233-41
    › Primary publication · 19928795 (PubMed) · PMC2797370 (PubMed Central)
  53. Progress toward the total synthesis of lucentamycin A: total synthesis and biological evaluation of 8-epi-lucentamycin A. Daniels RN, Melancon BJ, Wang EA, Crews BC, Marnett LJ, Sulikowski GA, Lindsley CW (2009) J Org Chem 74(22): 8852-5
    › Primary publication · 19908916 (PubMed)
  54. Repeated homotypic stress elevates 2-arachidonoylglycerol levels and enhances short-term endocannabinoid signaling at inhibitory synapses in basolateral amygdala. Patel S, Kingsley PJ, Mackie K, Marnett LJ, Winder DG (2009) Neuropsychopharmacology 34(13): 2699-709
    › Primary publication · 19675536 (PubMed) · PMC2881681 (PubMed Central)
  55. Differential sensitivity and mechanism of inhibition of COX-2 oxygenation of arachidonic acid and 2-arachidonoylglycerol by ibuprofen and mefenamic acid. Prusakiewicz JJ, Duggan KC, Rouzer CA, Marnett LJ (2009) Biochemistry 48(31): 7353-5
    › Primary publication · 19603831 (PubMed) · PMC2720641 (PubMed Central)
  56. Combined chemical and biosynthetic route to access a new apoptolidin congener. Ghidu VP, Ntai I, Wang J, Jacobs AT, Marnett LJ, Bachmann BO, Sulikowski GA (2009) Org Lett 11(14): 3032-4
    › Primary publication · 19552384 (PubMed) · PMC2720611 (PubMed Central)
  57. Analysis of endocannabinoids, their congeners and COX-2 metabolites. Kingsley PJ, Marnett LJ (2009) J Chromatogr B Analyt Technol Biomed Life Sci 877(26): 2746-54
    › Primary publication · 19505857 (PubMed) · PMC4903075 (PubMed Central)
  58. Structural and functional analysis of Sulfolobus solfataricus Y-family DNA polymerase Dpo4-catalyzed bypass of the malondialdehyde-deoxyguanosine adduct. Eoff RL, Stafford JB, Szekely J, Rizzo CJ, Egli M, Guengerich FP, Marnett LJ (2009) Biochemistry 48(30): 7079-88
    › Primary publication · 19492857 (PubMed) · PMC2717710 (PubMed Central)
  59. Synthesis of 5- and 6-carboxy-X-rhodamines. Uddin MJ, Marnett LJ (2008) Org Lett 10(21): 4799-801
    › Primary publication · 18837556 (PubMed) · PMC2646678 (PubMed Central)
  60. NMDA-induced seizure intensity is enhanced in COX-2 deficient mice. Toscano CD, Kingsley PJ, Marnett LJ, Bosetti F (2008) Neurotoxicology 29(6): 1114-20
    › Primary publication · 18834901 (PubMed) · PMC2587528 (PubMed Central)
  61. Structural basis of enantioselective inhibition of cyclooxygenase-1 by S-alpha-substituted indomethacin ethanolamides. Harman CA, Turman MV, Kozak KR, Marnett LJ, Smith WL, Garavito RM (2007) J Biol Chem 282(38): 28096-105
    › Primary publication · 17656360 (PubMed)
  62. Desmethyl derivatives of indomethacin and sulindac as probes for cyclooxygenase-dependent biology. Felts AS, Ji C, Stafford JB, Crews BC, Kingsley PJ, Rouzer CA, Washington MK, Subbaramaiah K, Siegel BS, Young SM, Dannenberg AJ, Marnett LJ (2007) ACS Chem Biol 2(7): 479-83
    › Primary publication · 17602619 (PubMed)