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Anthony Pegg

TitleProfessor Emeritus
InstitutionCollege of Medicine
DepartmentCellular and Molecular Physiology
Address500 University Drive Hershey PA 17033
Mailbox: H166
Phone7175318152

 Overview 
 overview
PREFERRED TITLE/ROLE:

Professor Emeritus, Evan Pugh Professor of Cellular and Molecular Physiology, and Pharmacology

SECONDARY APPOINTMENT(S)/ INSTITUTE(S)/ CENTER(S):

Pharmacology

GRADUATE PROGRAM AFFILIATIONS:

Cell and Molecular Biology, Integrative Biosciences, MD/PhD Degree Program, Physiology, Pharmacology

EDUCATION:

Ph.D., University of Cambridge, 1966
Postdoctoral Training, Johns Hopkins University Medical School, 1966-1968

NARRATIVE:

Polyamine Metabolism; DNA Repair

Research is being carried out on the cellular physiology of polyamines. Polyamines are small basic molecules essential for cell growth and differentiation. Their concentration is very tightly regulated within the cell and is altered by endocrine and other factors having trophic effects. The research is aimed at understanding metabolic pathways responsible for polyamine biosynthesis, degradation, and interconversion; factors responsible for regulating polyamine levels; polyamine roles in growth and differentiation; and design and application of specific inhibitors of polyamine production. Such inhibitors have already been shown to have potential therapeutic value and to be useful as research tools in studying polyamine function.

A second area of research concerns DNA repair enzymes' role in protecting against carcinogenesis by N-nitroso-compounds and other alkylating agents. An alkyltransferase, which removes alkyl groups from DNA, has been isolated and it has been shown that the level of this protein is both species and cell specific. There is a good correlation between the alkyltransferase content and resistance to carcinogenesis and mutagenesis by alkylating agents. Current research is aimed at studying the specificity of this system, factors controlling its activity, and investigating whether it is missing or reduced in certain hereditary conditions. Also, the possibility that transient inactivation of this DNA repair function can be used for cancer chemotherapy to augment the action of therapeutic alkylating agents is being investigated. A potent inhibitor, O6-benzylguanine, has been developed in Dr. Pegg's laboratory and in Phase 1 trials has been shown to be effective in depleting tumor cell alkyltransferase activity in patients with cancer. It is currently undergoing Phase 2 trials to determine its efficacy in improving chemotherapy.


 Bibliographic 
 selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Pegg AE. The function of spermine. IUBMB Life. 2014 Jan; 66(1):8-18.
    View in: PubMed
  2. Pegg AE. Toxicity of polyamines and their metabolic products. Chem Res Toxicol. 2013 Dec 16; 26(12):1782-800.
    View in: PubMed
  3. Chowdhury G, Cho SH, Pegg AE, Guengerich FP. Detection and characterization of 1,2-dibromoethane-derived DNA crosslinks formed with O(6) -alkylguanine-DNA alkyltransferase. Angew Chem Int Ed Engl. 2013 Dec 2; 52(49):12879-82.
    View in: PubMed
  4. Peterson LA, Urban AM, Vu CC, Cummings ME, Brown LC, Warmka JK, Li L, Wattenberg EV, Patel Y, Stram DO, Pegg AE. Role of aldehydes in the toxic and mutagenic effects of nitrosamines. Chem Res Toxicol. 2013 Oct 21; 26(10):1464-73.
    View in: PubMed
  5. Kotandeniya D, Murphy D, Yan S, Park S, Seneviratne U, Koopmeiners JS, Pegg A, Kanugula S, Kassie F, Tretyakova N. Kinetics of O(6)-pyridyloxobutyl-2'-deoxyguanosine repair by human O(6)-alkylguanine DNA alkyltransferase. Biochemistry. 2013 Jun 11; 52(23):4075-88.
    View in: PubMed
  6. Tretyakova NY, Michaelson-Richie ED, Gherezghiher TB, Kurtz J, Ming X, Wickramaratne S, Campion M, Kanugula S, Pegg AE, Campbell C. DNA-reactive protein monoepoxides induce cell death and mutagenesis in mammalian cells. Biochemistry. 2013 May 7; 52(18):3171-81.
    View in: PubMed
  7. Zhang Z, Zheng Y, Petukh M, Pegg A, Ikeguchi Y, Alexov E. Enhancing human spermine synthase activity by engineered mutations. PLoS Comput Biol. 2013; 9(2):e1002924.
    View in: PubMed
  8. Koomoa DL, Geerts D, Lange I, Koster J, Pegg AE, Feith DJ, Bachmann AS. DFMO/eflornithine inhibits migration and invasion downstream of MYCN and involves p27Kip1 activity in neuroblastoma. Int J Oncol. 2013 Apr; 42(4):1219-28.
    View in: PubMed
  9. Feith DJ, Pegg AE, Fong LY. Targeted expression of ornithine decarboxylase antizyme prevents upper aerodigestive tract carcinogenesis in p53-deficient mice. Carcinogenesis. 2013 Mar; 34(3):570-6.
    View in: PubMed
  10. Yamazaki K, Ikeguchi Y, Niwa T, Hayashi K, Iwaki T, Ishii I, Niitsu M, Pegg AE, Shirahata A. Determination of cellular aminopropyltransferase activity using precolumn fluorescent etheno-derivatization with high-performance liquid chromatography. Anal Sci. 2012; 28(6):621-4.
    View in: PubMed
  11. Kotandeniya D, Murphy D, Seneviratne U, Guza R, Pegg A, Kanugula S, Tretyakova N. Mass spectrometry based approach to study the kinetics of O6-alkylguanine DNA alkyltransferase-mediated repair of O6-pyridyloxobutyl-2'-deoxyguanosine adducts in DNA. Chem Res Toxicol. 2011 Nov 21; 24(11):1966-75.
    View in: PubMed
  12. Seckute J, McCloskey DE, Thomas HJ, Secrist JA, Pegg AE, Ealick SE. Binding and inhibition of human spermidine synthase by decarboxylated S-adenosylhomocysteine. Protein Sci. 2011 Nov; 20(11):1836-44.
    View in: PubMed
  13. Giordano E, Hillary RA, Vary TC, Pegg AE, Sumner AD, Caldarera CM, Zhang XQ, Song J, Wang J, Cheung JY, Shantz LM. Overexpression of ornithine decarboxylase decreases ventricular systolic function during induction of cardiac hypertrophy. Amino Acids. 2012 Feb; 42(2-3):507-18.
    View in: PubMed
  14. Ishii I, Ikeguchi Y, Mano H, Wada M, Pegg AE, Shirahata A. Polyamine metabolism is involved in adipogenesis of 3T3-L1 cells. Amino Acids. 2012 Feb; 42(2-3):619-26.
    View in: PubMed
  15. Shi C, Welsh PA, Sass-Kuhn S, Wang X, McCloskey DE, Pegg AE, Feith DJ. Characterization of transgenic mice with overexpression of spermidine synthase. Amino Acids. 2012 Feb; 42(2-3):495-505.
    View in: PubMed
  16. Green R, Hanfrey CC, Elliott KA, McCloskey DE, Wang X, Kanugula S, Pegg AE, Michael AJ. Independent evolutionary origins of functional polyamine biosynthetic enzyme fusions catalysing de novo diamine to triamine formation. Mol Microbiol. 2011 Aug; 81(4):1109-24.
    View in: PubMed
  17. Pegg AE. Multifaceted roles of alkyltransferase and related proteins in DNA repair, DNA damage, resistance to chemotherapy, and research tools. Chem Res Toxicol. 2011 May 16; 24(5):618-39.
    View in: PubMed
  18. Pegg AE, Wang X, Schwartz CE, McCloskey DE. Spermine synthase activity affects the content of decarboxylated S-adenosylmethionine. Biochem J. 2011 Jan 1; 433(1):139-44.
    View in: PubMed
  19. Wang X, Pegg AE. Use of (Gyro) Gy and spermine synthase transgenic mice to study functions of spermine. Methods Mol Biol. 2011; 720:159-70.
    View in: PubMed
  20. Pegg AE, Casero RA. Current status of the polyamine research field. Methods Mol Biol. 2011; 720:3-35.
    View in: PubMed
  21. Lee SB, Park JH, Folk JE, Deck JA, Pegg AE, Sokabe M, Fraser CS, Park MH. Inactivation of eukaryotic initiation factor 5A (eIF5A) by specific acetylation of its hypusine residue by spermidine/spermine acetyltransferase 1 (SSAT1). Biochem J. 2011 Jan 1; 433(1):205-13.
    View in: PubMed
  22. Schwartz CE, Wang X, Stevenson RE, Pegg AE. Spermine synthase deficiency resulting in X-linked intellectual disability (Snyder-Robinson syndrome). Methods Mol Biol. 2011; 720:437-45.
    View in: PubMed
  23. Saiki R, Park H, Ishii I, Yoshida M, Nishimura K, Toida T, Tatsukawa H, Kojima S, Ikeguchi Y, Pegg AE, Kashiwagi K, Igarashi K. Brain infarction correlates more closely with acrolein than with reactive oxygen species. Biochem Biophys Res Commun. 2011 Jan 28; 404(4):1044-9.
    View in: PubMed
  24. Chuk MK, Cole DE, McCully C, Loktionova NA, Pegg AE, Parker RJ, Pauly G, Widemann BC, Balis FM, Fox E. Plasma and CNS pharmacokinetics of O4-benzylfolic acid (O4BF) and metabolite in a non-human primate model. Cancer Chemother Pharmacol. 2011 Jun; 67(6):1291-7.
    View in: PubMed
  25. McManus FP, Fang Q, Booth JD, Noronha AM, Pegg AE, Wilds CJ. Synthesis and characterization of an O(6)-2'-deoxyguanosine-alkyl-O(6)-2'-deoxyguanosine interstrand cross-link in a 5'-GNC motif and repair by human O(6)-alkylguanine-DNA alkyltransferase. Org Biomol Chem. 2010 Oct 7; 8(19):4414-26.
    View in: PubMed
  26. Geerts D, Koster J, Albert D, Koomoa DL, Feith DJ, Pegg AE, Volckmann R, Caron H, Versteeg R, Bachmann AS. The polyamine metabolism genes ornithine decarboxylase and antizyme 2 predict aggressive behavior in neuroblastomas with and without MYCN amplification. Int J Cancer. 2010 May 1; 126(9):2012-24.
    View in: PubMed
  27. Aramini JM, Tubbs JL, Kanugula S, Rossi P, Ertekin A, Maglaqui M, Hamilton K, Ciccosanti CT, Jiang M, Xiao R, Soong TT, Rost B, Acton TB, Everett JK, Pegg AE, Tainer JA, Montelione GT. Structural basis of O6-alkylguanine recognition by a bacterial alkyltransferase-like DNA repair protein. J Biol Chem. 2010 Apr 30; 285(18):13736-41.
    View in: PubMed
  28. Bale S, Baba K, McCloskey DE, Pegg AE, Ealick SE. Complexes of Thermotoga maritimaS-adenosylmethionine decarboxylase provide insights into substrate specificity. Acta Crystallogr D Biol Crystallogr. 2010 Feb; 66(Pt 2):181-9.
    View in: PubMed
  29. Fang Q, Kanugula S, Tubbs JL, Tainer JA, Pegg AE. Repair of O4-alkylthymine by O6-alkylguanine-DNA alkyltransferases. J Biol Chem. 2010 Mar 12; 285(11):8185-95.
    View in: PubMed
  30. Kalapila AG, Pegg AE. Alkyltransferase-mediated toxicity of bis-electrophiles in mammalian cells. Mutat Res. 2010 Feb 3; 684(1-2):35-42.
    View in: PubMed
  31. Pegg AE. S-Adenosylmethionine decarboxylase. Essays Biochem. 2009; 46:25-45.
    View in: PubMed
  32. Pegg AE, Michael AJ. Spermine synthase. Cell Mol Life Sci. 2010 Jan; 67(1):113-21.
    View in: PubMed
  33. Pegg AE. Mammalian polyamine metabolism and function. IUBMB Life. 2009 Sep; 61(9):880-94.
    View in: PubMed
  34. Li L, Perdigao J, Pegg AE, Lao Y, Hecht SS, Lindgren BR, Reardon JT, Sancar A, Wattenberg EV, Peterson LA. The influence of repair pathways on the cytotoxicity and mutagenicity induced by the pyridyloxobutylation pathway of tobacco-specific nitrosamines. Chem Res Toxicol. 2009 Aug; 22(8):1464-72.
    View in: PubMed
  35. Casero RA, Pegg AE. Polyamine catabolism and disease. Biochem J. 2009 Aug 1; 421(3):323-38.
    View in: PubMed
  36. Koomoa DL, Borsics T, Feith DJ, Coleman CC, Wallick CJ, Gamper I, Pegg AE, Bachmann AS. Inhibition of S-adenosylmethionine decarboxylase by inhibitor SAM486A connects polyamine metabolism with p53-Mdm2-Akt/protein kinase B regulation and apoptosis in neuroblastoma. Mol Cancer Ther. 2009 Jul; 8(7):2067-75.
    View in: PubMed
  37. Kalapila AG, Loktionova NA, Pegg AE. Effect of O6-alkylguanine-DNA alkyltransferase on genotoxicity of epihalohydrins. Environ Mol Mutagen. 2009 Jul; 50(6):502-14.
    View in: PubMed
  38. Guza R, Ma L, Fang Q, Pegg AE, Tretyakova N. Cytosine methylation effects on the repair of O6-methylguanines within CG dinucleotides. J Biol Chem. 2009 Aug 21; 284(34):22601-10.
    View in: PubMed
  39. Tubbs JL, Latypov V, Kanugula S, Butt A, Melikishvili M, Kraehenbuehl R, Fleck O, Marriott A, Watson AJ, Verbeek B, McGown G, Thorncroft M, Santibanez-Koref MF, Millington C, Arvai AS, Kroeger MD, Peterson LA, Williams DM, Fried MG, Margison GP, Pegg AE, Tainer JA. Flipping of alkylated DNA damage bridges base and nucleotide excision repair. Nature. 2009 Jun 11; 459(7248):808-13.
    View in: PubMed
  40. Pegg AE, Wang X. Mouse models to investigate the function of spermine. Commun Integr Biol. 2009 May; 2(3):271-4.
    View in: PubMed
  41. Adams CA, Melikishvili M, Rodgers DW, Rasimas JJ, Pegg AE, Fried MG. Topologies of complexes containing O6-alkylguanine-DNA alkyltransferase and DNA. J Mol Biol. 2009 Jun 5; 389(2):248-63.
    View in: PubMed
  42. McCloskey DE, Bale S, Secrist JA, Tiwari A, Moss TH, Valiyaveettil J, Brooks WH, Guida WC, Pegg AE, Ealick SE. New insights into the design of inhibitors of human S-adenosylmethionine decarboxylase: studies of adenine C8 substitution in structural analogues of S-adenosylmethionine. J Med Chem. 2009 Mar 12; 52(5):1388-407.
    View in: PubMed
  43. Melikishvili M, Rasimas JJ, Pegg AE, Fried MG. Interactions of human O(6)-alkylguanine-DNA alkyltransferase (AGT) with short double-stranded DNAs. Biochemistry. 2008 Dec 30; 47(52):13754-63.
    View in: PubMed
  44. Bale S, Lopez MM, Makhatadze GI, Fang Q, Pegg AE, Ealick SE. Structural basis for putrescine activation of human S-adenosylmethionine decarboxylase. Biochemistry. 2008 Dec 16; 47(50):13404-17.
    View in: PubMed
  45. Philip S, Swaminathan S, Kuznetsov SG, Kanugula S, Biswas K, Chang S, Loktionova NA, Haines DC, Kaldis P, Pegg AE, Sharan SK. Degradation of BRCA2 in alkyltransferase-mediated DNA repair and its clinical implications. Cancer Res. 2008 Dec 1; 68(23):9973-81.
    View in: PubMed
  46. Pauly GT, Loktionova NA, Fang Q, Vankayala SL, Guida WC, Pegg AE. Substitution of aminomethyl at the meta-position enhances the inactivation of O6-alkylguanine-DNA alkyltransferase by O6-benzylguanine. J Med Chem. 2008 Nov 27; 51(22):7144-53.
    View in: PubMed
  47. Wang X, Levic S, Gratton MA, Doyle KJ, Yamoah EN, Pegg AE. Spermine synthase deficiency leads to deafness and a profound sensitivity to alpha-difluoromethylornithine. J Biol Chem. 2009 Jan 9; 284(2):930-7.
    View in: PubMed
  48. Fang Q, Noronha AM, Murphy SP, Wilds CJ, Tubbs JL, Tainer JA, Chowdhury G, Guengerich FP, Pegg AE. Repair of O6-G-alkyl-O6-G interstrand cross-links by human O6-alkylguanine-DNA alkyltransferase. Biochemistry. 2008 Oct 14; 47(41):10892-903.
    View in: PubMed
  49. Kalapila AG, Loktionova NA, Pegg AE. Alkyltransferase-mediated toxicity of 1,3-butadiene diepoxide. Chem Res Toxicol. 2008 Sep; 21(9):1851-61.
    View in: PubMed
  50. deHart GW, Jin T, McCloskey DE, Pegg AE, Sheppard D. The alpha9beta1 integrin enhances cell migration by polyamine-mediated modulation of an inward-rectifier potassium channel. Proc Natl Acad Sci U S A. 2008 May 20; 105(20):7188-93.
    View in: PubMed
  51. Wu H, Min J, Zeng H, McCloskey DE, Ikeguchi Y, Loppnau P, Michael AJ, Pegg AE, Plotnikov AN. Crystal structure of human spermine synthase: implications of substrate binding and catalytic mechanism. J Biol Chem. 2008 Jun 6; 283(23):16135-46.
    View in: PubMed
  52. Soriano EV, McCloskey DE, Kinsland C, Pegg AE, Ealick SE. Structures of the N47A and E109Q mutant proteins of pyruvoyl-dependent arginine decarboxylase from Methanococcus jannaschii. Acta Crystallogr D Biol Crystallogr. 2008 Apr; 64(Pt 4):377-82.
    View in: PubMed
  53. Pegg AE. Spermidine/spermine-N(1)-acetyltransferase: a key metabolic regulator. Am J Physiol Endocrinol Metab. 2008 Jun; 294(6):E995-1010.
    View in: PubMed
  54. Loeber R, Michaelson E, Fang Q, Campbell C, Pegg AE, Tretyakova N. Cross-linking of the DNA repair protein Omicron6-alkylguanine DNA alkyltransferase to DNA in the presence of antitumor nitrogen mustards. Chem Res Toxicol. 2008 Apr; 21(4):787-95.
    View in: PubMed
  55. Mumenthaler SM, Yu H, Tze S, Cederbaum SD, Pegg AE, Seligson DB, Grody WW. Expression of arginase II in prostate cancer. Int J Oncol. 2008 Feb; 32(2):357-65.
    View in: PubMed
  56. Coulter R, Blandino M, Tomlinson JM, Pauly GT, Krajewska M, Moschel RC, Peterson LA, Pegg AE, Spratt TE. Differences in the rate of repair of O6-alkylguanines in different sequence contexts by O6-alkylguanine-DNA alkyltransferase. Chem Res Toxicol. 2007 Dec; 20(12):1966-71.
    View in: PubMed
  57. Fang Q, Loktionova NA, Moschel RC, Javanmard S, Pauly GT, Pegg AE. Differential inactivation of polymorphic variants of human O6-alkylguanine-DNA alkyltransferase. Biochem Pharmacol. 2008 Feb 1; 75(3):618-26.
    View in: PubMed
  58. Javanmard S, Loktionova NA, Fang Q, Pauly GT, Pegg AE, Moschel RC. Inactivation of O(6)-alkylguanine-DNA alkyltransferase by folate esters of O(6)-benzyl-2'-deoxyguanosine and of O(6)-[4-(hydroxymethyl)benzyl]guanine. J Med Chem. 2007 Oct 18; 50(21):5193-201.
    View in: PubMed
  59. Deignan JL, Livesay JC, Shantz LM, Pegg AE, O'Brien WE, Iyer RK, Cederbaum SD, Grody WW. Polyamine homeostasis in arginase knockout mice. Am J Physiol Cell Physiol. 2007 Oct; 293(4):C1296-301.
    View in: PubMed
  60. Brooks WH, McCloskey DE, Daniel KG, Ealick SE, Secrist JA, Waud WR, Pegg AE, Guida WC. In silico chemical library screening and experimental validation of a novel 9-aminoacridine based lead-inhibitor of human S-adenosylmethionine decarboxylase. J Chem Inf Model. 2007 Sep-Oct; 47(5):1897-905.
    View in: PubMed
  61. Wang X, Feith DJ, Welsh P, Coleman CS, Lopez C, Woster PM, O'Brien TG, Pegg AE. Studies of the mechanism by which increased spermidine/spermine N1-acetyltransferase activity increases susceptibility to skin carcinogenesis. Carcinogenesis. 2007 Nov; 28(11):2404-11.
    View in: PubMed
  62. Wu H, Min J, Ikeguchi Y, Zeng H, Dong A, Loppnau P, Pegg AE, Plotnikov AN. Structure and mechanism of spermidine synthases. Biochemistry. 2007 Jul 17; 46(28):8331-9.
    View in: PubMed
  63. Feith DJ, Shantz LM, Shoop PL, Keefer KA, Prakashagowda C, Pegg AE. Mouse skin chemical carcinogenesis is inhibited by antizyme in promotion-sensitive and promotion-resistant genetic backgrounds. Mol Carcinog. 2007 Jun; 46(6):453-65.
    View in: PubMed
  64. Hansen RJ, Ludeman SM, Paikoff SJ, Pegg AE, Dolan ME. Role of MGMT in protecting against cyclophosphamide-induced toxicity in cells and animals. DNA Repair (Amst). 2007 Aug 1; 6(8):1145-54.
    View in: PubMed
  65. Tubbs JL, Pegg AE, Tainer JA. DNA binding, nucleotide flipping, and the helix-turn-helix motif in base repair by O6-alkylguanine-DNA alkyltransferase and its implications for cancer chemotherapy. DNA Repair (Amst). 2007 Aug 1; 6(8):1100-15.
    View in: PubMed
  66. Pegg AE, Fang Q, Loktionova NA. Human variants of O6-alkylguanine-DNA alkyltransferase. DNA Repair (Amst). 2007 Aug 1; 6(8):1071-8.
    View in: PubMed
  67. Pegg AE, Feith DJ. Polyamines and neoplastic growth. Biochem Soc Trans. 2007 Apr; 35(Pt 2):295-9.
    View in: PubMed
  68. Liu L, Watanabe K, Fang Q, Williams KM, Guengerich FP, Pegg AE. Effect of alterations of key active site residues in O6-alkylguanine-DNA Alkyltransferase on its ability to modulate the genotoxicity of 1,2-dibromoethane. Chem Res Toxicol. 2007 Jan; 20(1):155-63.
    View in: PubMed
  69. Rasimas JJ, Kar SR, Pegg AE, Fried MG. Interactions of human O6-alkylguanine-DNA alkyltransferase (AGT) with short single-stranded DNAs. J Biol Chem. 2007 Feb 2; 282(5):3357-66.
    View in: PubMed
  70. Loeber R, Rajesh M, Fang Q, Pegg AE, Tretyakova N. Cross-linking of the human DNA repair protein O6-alkylguanine DNA alkyltransferase to DNA in the presence of 1,2,3,4-diepoxybutane. Chem Res Toxicol. 2006 May; 19(5):645-54.
    View in: PubMed
  71. Mijal RS, Kanugula S, Vu CC, Fang Q, Pegg AE, Peterson LA. DNA sequence context affects repair of the tobacco-specific adduct O(6)-[4-Oxo-4-(3-pyridyl)butyl]guanine by human O(6)-alkylguanine-DNA alkyltransferases. Cancer Res. 2006 May 1; 66(9):4968-74.
    View in: PubMed
  72. Guza R, Rajesh M, Fang Q, Pegg AE, Tretyakova N. Kinetics of O(6)-methyl-2'-deoxyguanosine repair by O(6)-alkylguanine DNA alkyltransferase within K-ras gene-derived DNA sequences. Chem Res Toxicol. 2006 Apr; 19(4):531-8.
    View in: PubMed
  73. Pegg AE. Regulation of ornithine decarboxylase. J Biol Chem. 2006 May 26; 281(21):14529-32.
    View in: PubMed
  74. Bewley MC, Graziano V, Jiang J, Matz E, Studier FW, Pegg AE, Coleman CS, Flanagan JM. Structures of wild-type and mutant human spermidine/spermine N1-acetyltransferase, a potential therapeutic drug target. Proc Natl Acad Sci U S A. 2006 Feb 14; 103(7):2063-8.
    View in: PubMed
  75. Fontes AM, Davis BM, Encell LP, Lingas K, Covas DT, Zago MA, Loeb LA, Pegg AE, Gerson SL. Differential competitive resistance to methylating versus chloroethylating agents among five O6-alkylguanine DNA alkyltransferases in human hematopoietic cells. Mol Cancer Ther. 2006 Jan; 5(1):121-8.
    View in: PubMed
  76. Ikeguchi Y, Bewley MC, Pegg AE. Aminopropyltransferases: function, structure and genetics. J Biochem. 2006 Jan; 139(1):1-9.
    View in: PubMed
  77. Nisenberg O, Pegg AE, Welsh PA, Keefer K, Shantz LM. Overproduction of cardiac S-adenosylmethionine decarboxylase in transgenic mice. Biochem J. 2006 Jan 1; 393(Pt 1):295-302.
    View in: PubMed
  78. Fang Q, Kanugula S, Pegg AE. Function of domains of human O6-alkylguanine-DNA alkyltransferase. Biochemistry. 2005 Nov 22; 44(46):15396-405.
    View in: PubMed
  79. Mijal RS, Loktionova NA, Vu CC, Pegg AE, Peterson LA. O6-pyridyloxobutylguanine adducts contribute to the mutagenic properties of pyridyloxobutylating agents. Chem Res Toxicol. 2005 Oct; 18(10):1619-25.
    View in: PubMed
  80. Quinn JA, Desjardins A, Weingart J, Brem H, Dolan ME, Delaney SM, Vredenburgh J, Rich J, Friedman AH, Reardon DA, Sampson JH, Pegg AE, Moschel RC, Birch R, McLendon RE, Provenzale JM, Gururangan S, Dancey JE, Maxwell J, Tourt-Uhlig S, Herndon JE, Bigner DD, Friedman HS. Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma. J Clin Oncol. 2005 Oct 1; 23(28):7178-87.
    View in: PubMed
  81. Wallick CJ, Gamper I, Thorne M, Feith DJ, Takasaki KY, Wilson SM, Seki JA, Pegg AE, Byus CV, Bachmann AS. Key role for p27Kip1, retinoblastoma protein Rb, and MYCN in polyamine inhibitor-induced G1 cell cycle arrest in MYCN-amplified human neuroblastoma cells. Oncogene. 2005 Aug 25; 24(36):5606-18.
    View in: PubMed
  82. Zang H, Fang Q, Pegg AE, Guengerich FP. Kinetic analysis of steps in the repair of damaged DNA by human O6-alkylguanine-DNA alkyltransferase. J Biol Chem. 2005 Sep 2; 280(35):30873-81.
    View in: PubMed
  83. Marverti G, Giuseppina Monti M, Pegg AE, McCloskey DE, Bettuzzi S, Ligabue A, Caporali A, D'Arca D, Moruzzi MS. Spermidine/spermine N1-acetyltransferase transient overexpression restores sensitivity of resistant human ovarian cancer cells to N1,N12-bis(ethyl)spermine and to cisplatin. Carcinogenesis. 2005 Oct; 26(10):1677-86.
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  84. Kanugula S, Pauly GT, Moschel RC, Pegg AE. A bifunctional DNA repair protein from Ferroplasma acidarmanus exhibits O6-alkylguanine-DNA alkyltransferase and endonuclease V activities. Proc Natl Acad Sci U S A. 2005 Mar 8; 102(10):3617-22.
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  85. Ackermann JM, Kanugula S, Pegg AE. DNAzyme-mediated silencing of ornithine decarboxylase. Biochemistry. 2005 Feb 15; 44(6):2143-52.
    View in: PubMed
  86. Wei G, Loktionova NA, Pegg AE, Moschel RC. Beta-glucuronidase-cleavable prodrugs of O6-benzylguanine and O6-benzyl-2'-deoxyguanosine. J Med Chem. 2005 Jan 13; 48(1):256-61.
    View in: PubMed
  87. Thomson NM, Mijal RS, Ziegel R, Fleischer NL, Pegg AE, Tretyakova NY, Peterson LA. Development of a quantitative liquid chromatography/electrospray mass spectrometric assay for a mutagenic tobacco specific nitrosamine-derived DNA adduct, O6-[4-Oxo-4-(3-pyridyl)butyl]-2'-deoxyguanosine. Chem Res Toxicol. 2004 Dec; 17(12):1600-6.
    View in: PubMed
  88. Coleman CS, Stanley BA, Jones AD, Pegg AE. Spermidine/spermine-N1-acetyltransferase-2 (SSAT2) acetylates thialysine and is not involved in polyamine metabolism. Biochem J. 2004 Nov 15; 384(Pt 1):139-48.
    View in: PubMed
  89. Levin VA, Jochec JL, Shantz LM, Koch PE, Pegg AE. Tissue-based assay for ornithine decarboxylase to identify patients likely to respond to difluoromethylornithine. J Histochem Cytochem. 2004 Nov; 52(11):1467-74.
    View in: PubMed
  90. Chen C, Young BA, Coleman CS, Pegg AE, Sheppard D. Spermidine/spermine N1-acetyltransferase specifically binds to the integrin alpha9 subunit cytoplasmic domain and enhances cell migration. J Cell Biol. 2004 Oct 11; 167(1):161-70.
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  91. Wang X, Ikeguchi Y, McCloskey DE, Nelson P, Pegg AE. Spermine synthesis is required for normal viability, growth, and fertility in the mouse. J Biol Chem. 2004 Dec 3; 279(49):51370-5.
    View in: PubMed
  92. Bacolod MD, Johnson SP, Pegg AE, Dolan ME, Moschel RC, Bullock NS, Fang Q, Colvin OM, Modrich P, Bigner DD, Friedman HS. Brain tumor cell lines resistant to O6-benzylguanine/1,3-bis(2-chloroethyl)-1-nitrosourea chemotherapy have O6-alkylguanine-DNA alkyltransferase mutations. Mol Cancer Ther. 2004 Sep; 3(9):1127-35.
    View in: PubMed
  93. Ikeguchi Y, Wang X, McCloskey DE, Coleman CS, Nelson P, Hu G, Shantz LM, Pegg AE. Characterization of transgenic mice with widespread overexpression of spermine synthase. Biochem J. 2004 Aug 1; 381(Pt 3):701-7.
    View in: PubMed
  94. Choi U, DeRavin SS, Yamashita K, Whiting-Theobald N, Linton GF, Loktionova NA, Pegg AE, Malech HL. Nuclear-localizing O6-benzylguanine-resistant GFP-MGMT fusion protein as a novel in vivo selection marker. Exp Hematol. 2004 Aug; 32(8):709-19.
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  95. Nelson ME, Loktionova NA, Pegg AE, Moschel RC. 2-amino-O4-benzylpteridine derivatives: potent inactivators of O6-alkylguanine-DNA alkyltransferase. J Med Chem. 2004 Jul 15; 47(15):3887-91.
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  96. Valadez JG, Liu L, Loktionova NA, Pegg AE, Guengerich FP. Activation of bis-electrophiles to mutagenic conjugates by human O6-alkylguanine-DNA alkyltransferase. Chem Res Toxicol. 2004 Jul; 17(7):972-82.
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  97. Daniels DS, Woo TT, Luu KX, Noll DM, Clarke ND, Pegg AE, Tainer JA. DNA binding and nucleotide flipping by the human DNA repair protein AGT. Nat Struct Mol Biol. 2004 Aug; 11(8):714-20.
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  98. Shah R, Coleman CS, Mir K, Baldwin J, Van Etten JL, Grishin NV, Pegg AE, Stanley BA, Phillips MA. Paramecium bursaria chlorella virus-1 encodes an unusual arginine decarboxylase that is a close homolog of eukaryotic ornithine decarboxylases. J Biol Chem. 2004 Aug 20; 279(34):35760-7.
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  99. Liu L, Williams KM, Guengerich FP, Pegg AE. O6-alkylguanine-DNA alkyltransferase has opposing effects in modulating the genotoxicity of dibromomethane and bromomethyl acetate. Chem Res Toxicol. 2004 Jun; 17(6):742-52.
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  100. Toms AV, Kinsland C, McCloskey DE, Pegg AE, Ealick SE. Evolutionary links as revealed by the structure of Thermotoga maritima S-adenosylmethionine decarboxylase. J Biol Chem. 2004 Aug 6; 279(32):33837-46.
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  101. Gabrielson E, Tully E, Hacker A, Pegg AE, Davidson NE, Casero RA. Induction of spermidine/spermine N1-acetyltransferase in breast cancer tissues treated with the polyamine analogue N1, N11-diethylnorspermine. Cancer Chemother Pharmacol. 2004 Aug; 54(2):122-6.
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  102. Coleman CS, Hu G, Pegg AE. Putrescine biosynthesis in mammalian tissues. Biochem J. 2004 May 1; 379(Pt 3):849-55.
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  103. Tang X, Kim AL, Feith DJ, Pegg AE, Russo J, Zhang H, Aszterbaum M, Kopelovich L, Epstein EH, Bickers DR, Athar M. Ornithine decarboxylase is a target for chemoprevention of basal and squamous cell carcinomas in Ptch1+/- mice. J Clin Invest. 2004 Mar; 113(6):867-75.
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  104. Mijal RS, Thomson NM, Fleischer NL, Pauly GT, Moschel RC, Kanugula S, Fang Q, Pegg AE, Peterson LA. The repair of the tobacco specific nitrosamine derived adduct O6-[4-Oxo-4-(3-pyridyl)butyl]guanine by O6-alkylguanine-DNA alkyltransferase variants. Chem Res Toxicol. 2004 Mar; 17(3):424-34.
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  105. Rasimas JJ, Dalessio PA, Ropson IJ, Pegg AE, Fried MG. Active-site alkylation destabilizes human O6-alkylguanine DNA alkyltransferase. Protein Sci. 2004 Jan; 13(1):301-5.
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  106. Cason AL, Ikeguchi Y, Skinner C, Wood TC, Holden KR, Lubs HA, Martinez F, Simensen RJ, Stevenson RE, Pegg AE, Schwartz CE. X-linked spermine synthase gene (SMS) defect: the first polyamine deficiency syndrome. Eur J Hum Genet. 2003 Dec; 11(12):937-44.
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  107. Liu L, Hachey DL, Valadez G, Williams KM, Guengerich FP, Loktionova NA, Kanugula S, Pegg AE. Characterization of a mutagenic DNA adduct formed from 1,2-dibromoethane by O6-alkylguanine-DNA alkyltransferase. J Biol Chem. 2004 Feb 6; 279(6):4250-9.
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  108. Meyer AS, McCain MD, Fang Q, Pegg AE, Spratt TE. O6-alkylguanine-DNA alkyltransferases repair O6-methylguanine in DNA with Michaelis-Menten-like kinetics. Chem Res Toxicol. 2003 Nov; 16(11):1405-9.
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  109. Kanugula S, Pegg AE. Alkylation damage repair protein O6-alkylguanine-DNA alkyltransferase from the hyperthermophiles Aquifex aeolicus and Archaeoglobus fulgidus. Biochem J. 2003 Oct 15; 375(Pt 2):449-55.
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  110. Guengerich FP, Fang Q, Liu L, Hachey DL, Pegg AE. O6-alkylguanine-DNA alkyltransferase: low pKa and high reactivity of cysteine 145. Biochemistry. 2003 Sep 23; 42(37):10965-70.
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  111. Kokkinakis DM, Ahmed MM, Chendil D, Moschel RC, Pegg AE. Sensitization of pancreatic tumor xenografts to carmustine and temozolomide by inactivation of their O6-Methylguanine-DNA methyltransferase with O6-benzylguanine or O6-benzyl-2'-deoxyguanosine. Clin Cancer Res. 2003 Sep 1; 9(10 Pt 1):3801-7.
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  112. Ikeguchi Y, Mackintosh CA, McCloskey DE, Pegg AE. Effect of spermine synthase on the sensitivity of cells to anti-tumour agents. Biochem J. 2003 Aug 1; 373(Pt 3):885-92.
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  113. Fong LY, Feith DJ, Pegg AE. Antizyme overexpression in transgenic mice reduces cell proliferation, increases apoptosis, and reduces N-nitrosomethylbenzylamine-induced forestomach carcinogenesis. Cancer Res. 2003 Jul 15; 63(14):3945-54.
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  114. Hillary RA, Pegg AE. Decarboxylases involved in polyamine biosynthesis and their inactivation by nitric oxide. Biochim Biophys Acta. 2003 Apr 11; 1647(1-2):161-6.
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  115. Pegg AE, Feith DJ, Fong LY, Coleman CS, O'Brien TG, Shantz LM. Transgenic mouse models for studies of the role of polyamines in normal, hypertrophic and neoplastic growth. Biochem Soc Trans. 2003 Apr; 31(2):356-60.
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  116. Tolbert WD, Zhang Y, Cottet SE, Bennett EM, Ekstrom JL, Pegg AE, Ealick SE. Mechanism of human S-adenosylmethionine decarboxylase proenzyme processing as revealed by the structure of the S68A mutant. Biochemistry. 2003 Mar 4; 42(8):2386-95.
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  117. McCloskey DE, Pegg AE. Properties of the spermidine/spermine N1-acetyltransferase mutant L156F that decreases cellular sensitivity to the polyamine analogue N1, N11-bis(ethyl)norspermine. J Biol Chem. 2003 Apr 18; 278(16):13881-7.
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  118. Rasimas JJ, Kanugula S, Dalessio PM, Ropson IJ, Fried MG, Pegg AE. Effects of zinc occupancy on human O6-alkylguanine-DNA alkyltransferase. Biochemistry. 2003 Feb 4; 42(4):980-90.
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  119. Ackermann JM, Pegg AE, McCloskey DE. Drugs affecting the cell cycle via actions on the polyamine metabolic pathway. Prog Cell Cycle Res. 2003; 5:461-8.
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  120. Rasimas JJ, Pegg AE, Fried MG. DNA-binding mechanism of O6-alkylguanine-DNA alkyltransferase. Effects of protein and DNA alkylation on complex stability. J Biol Chem. 2003 Mar 7; 278(10):7973-80.
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  121. Bennett EM, Ekstrom JL, Pegg AE, Ealick SE. Monomeric S-adenosylmethionine decarboxylase from plants provides an alternative to putrescine stimulation. Biochemistry. 2002 Dec 10; 41(49):14509-17.
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  122. Stefanelli C, Tantini B, Fattori M, Stanic' I, Pignatti C, Clo C, Guarnieri C, Caldarera CM, Mackintosh CA, Pegg AE, Flamigni F. Caspase activation in etoposide-treated fibroblasts is correlated to ERK phosphorylation and both events are blocked by polyamine depletion. FEBS Lett. 2002 Sep 11; 527(1-3):223-28.
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  123. Friedman HS, Keir S, Pegg AE, Houghton PJ, Colvin OM, Moschel RC, Bigner DD, Dolan ME. O6-benzylguanine-mediated enhancement of chemotherapy. Mol Cancer Ther. 2002 Sep; 1(11):943-8.
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  124. Liu L, Pegg AE, Williams KM, Guengerich FP. Paradoxical enhancement of the toxicity of 1,2-dibromoethane by O6-alkylguanine-DNA alkyltransferase. J Biol Chem. 2002 Oct 4; 277(40):37920-8.
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  125. Luu KX, Kanugula S, Pegg AE, Pauly GT, Moschel RC. Repair of oligodeoxyribonucleotides by O(6)-alkylguanine-DNA alkyltransferase. Biochemistry. 2002 Jul 9; 41(27):8689-97.
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  126. Liu L, Xu-Welliver M, Kanugula S, Pegg AE. Inactivation and degradation of O(6)-alkylguanine-DNA alkyltransferase after reaction with nitric oxide. Cancer Res. 2002 Jun 1; 62(11):3037-43.
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  127. Xu-Welliver M, Pegg AE. Degradation of the alkylated form of the DNA repair protein, O(6)-alkylguanine-DNA alkyltransferase. Carcinogenesis. 2002 May; 23(5):823-30.
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  128. Quinn JA, Pluda J, Dolan ME, Delaney S, Kaplan R, Rich JN, Friedman AH, Reardon DA, Sampson JH, Colvin OM, Haglund MM, Pegg AE, Moschel RC, McLendon RE, Provenzale JM, Gururangan S, Tourt-Uhlig S, Herndon JE, Bigner DD, Friedman HS. Phase II trial of carmustine plus O(6)-benzylguanine for patients with nitrosourea-resistant recurrent or progressive malignant glioma. J Clin Oncol. 2002 May 1; 20(9):2277-83.
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  129. Loktionova NA, Pegg AE. Interaction of mammalian O(6)-alkylguanine-DNA alkyltransferases with O(6)-benzylguanine. Biochem Pharmacol. 2002 Apr 15; 63(8):1431-42.
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  130. Shantz LM, Guo Y, Sawicki JA, Pegg AE, O'Brien TG. Overexpression of a dominant-negative ornithine decarboxylase in mouse skin: effect on enzyme activity and papilloma formation. Carcinogenesis. 2002 Apr; 23(4):657-64.
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  131. Coleman CS, Pegg AE, Megosh LC, Guo Y, Sawicki JA, O'Brien TG. Targeted expression of spermidine/spermine N1-acetyltransferase increases susceptibility to chemically induced skin carcinogenesis. Carcinogenesis. 2002 Feb; 23(2):359-64.
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  132. Korolev S, Ikeguchi Y, Skarina T, Beasley S, Arrowsmith C, Edwards A, Joachimiak A, Pegg AE, Savchenko A. The crystal structure of spermidine synthase with a multisubstrate adduct inhibitor. Nat Struct Biol. 2002 Jan; 9(1):27-31.
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  133. Pegg AE, Goodtzova K, Loktionova NA, Kanugula S, Pauly GT, Moschel RC. Inactivation of human O(6)-alkylguanine-DNA alkyltransferase by modified oligodeoxyribonucleotides containing O(6)-benzylguanine. J Pharmacol Exp Ther. 2001 Mar; 296(3):958-65.
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  134. Pegg AE. Repair of O(6)-alkylguanine by alkyltransferases. Mutat Res. 2000 Apr; 462(2-3):83-100.
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