ANTHONY PEGG

Summary

Affiliation: Pennsylvania State University
Country: USA

Publications

  1. ncbi request reprint Inactivation of human O(6)-alkylguanine-DNA alkyltransferase by modified oligodeoxyribonucleotides containing O(6)-benzylguanine
    A E Pegg
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, The Milton S Hershey Medical Center, Hershey, Pennsylvania 17033, USA
    J Pharmacol Exp Ther 296:958-65. 2001
  2. ncbi request reprint Repair of O(6)-alkylguanine by alkyltransferases
    A E Pegg
    Departments of Cellular and Molecular Physiology and Pharmacology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, P O Box 850, 500 University Drive, Hershey, PA, USA
    Mutat Res 462:83-100. 2000
  3. doi request reprint Spermine synthase activity affects the content of decarboxylated S-adenosylmethionine
    Anthony E Pegg
    Department of Cellular and Molecular Physiology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, PA 17033, USA
    Biochem J 433:139-44. 2011
  4. pmc Multifaceted roles of alkyltransferase and related proteins in DNA repair, DNA damage, resistance to chemotherapy, and research tools
    Anthony E Pegg
    Department of Cellular and Molecular Physiology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, Pennsylvania 17033, United States
    Chem Res Toxicol 24:618-39. 2011
  5. doi request reprint S-Adenosylmethionine decarboxylase
    Anthony E Pegg
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Essays Biochem 46:25-45. 2009
  6. pmc Spermine synthase
    Anthony E Pegg
    Department of Cellular and Molecular Physiology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Cell Mol Life Sci 67:113-21. 2010
  7. pmc Mammalian polyamine metabolism and function
    Anthony E Pegg
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    IUBMB Life 61:880-94. 2009
  8. ncbi request reprint Regulation of ornithine decarboxylase
    Anthony E Pegg
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    J Biol Chem 281:14529-32. 2006
  9. ncbi request reprint Transgenic mouse models for studies of the role of polyamines in normal, hypertrophic and neoplastic growth
    A E Pegg
    Department of Cellular and Molecular Physiology, The Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, P O Box 850, Hershey, PA 17033, U S A
    Biochem Soc Trans 31:356-60. 2003
  10. ncbi request reprint Polyamines and neoplastic growth
    A E Pegg
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Biochem Soc Trans 35:295-9. 2007

Collaborators

Detail Information

Publications96

  1. ncbi request reprint Inactivation of human O(6)-alkylguanine-DNA alkyltransferase by modified oligodeoxyribonucleotides containing O(6)-benzylguanine
    A E Pegg
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, The Milton S Hershey Medical Center, Hershey, Pennsylvania 17033, USA
    J Pharmacol Exp Ther 296:958-65. 2001
    ..These results suggest that oligodeoxyribonucleotides such as 11-mpBG may prove to be useful drugs for potentiation of alkylating agent chemotherapy if uptake can be improved...
  2. ncbi request reprint Repair of O(6)-alkylguanine by alkyltransferases
    A E Pegg
    Departments of Cellular and Molecular Physiology and Pharmacology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, P O Box 850, 500 University Drive, Hershey, PA, USA
    Mutat Res 462:83-100. 2000
    ..Several polymorphisms in the human alkyltransferase gene have been identified but the significance of these in terms of alkyltransferase action is currently unknown...
  3. doi request reprint Spermine synthase activity affects the content of decarboxylated S-adenosylmethionine
    Anthony E Pegg
    Department of Cellular and Molecular Physiology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, PA 17033, USA
    Biochem J 433:139-44. 2011
    ....
  4. pmc Multifaceted roles of alkyltransferase and related proteins in DNA repair, DNA damage, resistance to chemotherapy, and research tools
    Anthony E Pegg
    Department of Cellular and Molecular Physiology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, Pennsylvania 17033, United States
    Chem Res Toxicol 24:618-39. 2011
    ..Such proteins occur naturally, and synthetic variants engineered to react specifically with derivatives of O(6)-benzylguanine are the basis of a valuable research technique for tagging proteins with specific reagents...
  5. doi request reprint S-Adenosylmethionine decarboxylase
    Anthony E Pegg
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Essays Biochem 46:25-45. 2009
    ..The intricate mechanisms for regulation of mammalian S-adenosylmethionine decarboxylase activity and content are also described...
  6. pmc Spermine synthase
    Anthony E Pegg
    Department of Cellular and Molecular Physiology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Cell Mol Life Sci 67:113-21. 2010
    ..Mutations in the human SMS lead to a rise in spermidine and reduction of spermine causing Snyder-Robinson syndrome, an X-linked recessive condition characterized by mental retardation, skeletal defects, hypotonia, and movement disorders...
  7. pmc Mammalian polyamine metabolism and function
    Anthony E Pegg
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    IUBMB Life 61:880-94. 2009
    ..This review will summarize the current state of understanding of polyamine metabolism and function, the regulation of polyamine content, and heritable pathological conditions that may be derived from altered polyamine metabolism...
  8. ncbi request reprint Regulation of ornithine decarboxylase
    Anthony E Pegg
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    J Biol Chem 281:14529-32. 2006
    ..This review describes key factors that contribute to the regulation of ODC levels, which can occur at the levels of transcription, translation, and protein turnover...
  9. ncbi request reprint Transgenic mouse models for studies of the role of polyamines in normal, hypertrophic and neoplastic growth
    A E Pegg
    Department of Cellular and Molecular Physiology, The Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, P O Box 850, Hershey, PA 17033, U S A
    Biochem Soc Trans 31:356-60. 2003
    ....
  10. ncbi request reprint Polyamines and neoplastic growth
    A E Pegg
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Biochem Soc Trans 35:295-9. 2007
    ....
  11. pmc Human variants of O6-alkylguanine-DNA alkyltransferase
    Anthony E Pegg
    Department of Cellular and Molecular Physiology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA
    DNA Repair (Amst) 6:1071-8. 2007
    ....
  12. pmc Regulation of S-adenosylmethionine decarboxylase activity by alterations in the intracellular polyamine content
    L M Shantz
    Department of Cellular and Molecular Physiology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033
    Biochem J 288:511-8. 1992
    ..DFMO treatment did not interfere with the expression of plasmids driven by the RSV promoter. These results suggest that low spermidine levels interfere with the replication of plasmids containing the SV40 origin of replication...
  13. pmc Structure and critical residues at the active site of spermidine/spermine-N1-acetyltransferase
    C S Coleman
    Department of Cellular and Molecular Physiology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033, USA
    Biochem J 316:697-701. 1996
    ..These results indicate that the double mutant R101A/E152K-SSAT protein can be used to evaluate the importance of SSAT activity in response to exogenous polyamines or polyamine analogues...
  14. pmc Effects of chronic 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxy- adenosine (AbeAdo) treatment on polyamine and eIF-5A metabolism in AbeAdo-sensitive and -resistant L1210 murine leukaemia cells
    T L Byers
    Department of Cellular and Molecular Physiology, M S Hershey Medical Center, Hershey, PA 17033
    Biochem J 290:115-21. 1993
    ....
  15. pmc The role of hypusine depletion in cytostasis induced by S-adenosyl-L-methionine decarboxylase inhibition: new evidence provided by 1-methylspermidine and 1,12-dimethylspermine
    T L Byers
    Department of Cell and Molecular Physiology, M S Hershey Medical Center, Hershey, PA 17033
    Biochem J 303:363-8. 1994
    ..J. 290, 115-121] that AbeAdo-induced cytostasis is due to the depletion of the hypusine-containing form of eIF-5A, which is secondary to the depletion of spermidine by inhibition of S-adenosyl-L-methionine decarboxylase...
  16. ncbi request reprint Targeted antizyme expression in the skin of transgenic mice reduces tumor promoter induction of ornithine decarboxylase and decreases sensitivity to chemical carcinogenesis
    D J Feith
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Cancer Res 61:6073-81. 2001
    ..These mice demonstrate for the first time that AZ suppresses tumor growth in an animal cancer model and provide a valuable model system to evaluate the role of ODC and polyamines in skin tumorigenesis...
  17. ncbi request reprint DNA binding mechanism of O6-alkylguanine-DNA alkyltransferase: stoichiometry and effects of DNA base composition and secondary structure on complex stability
    M G Fried
    Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey 17033, USA
    Biochemistry 35:15295-301. 1996
    ..These results suggest mechanisms by which AGT may search for alkylated sites and interact with them to effect DNA repair...
  18. pmc Polyamine analogues inhibit the ubiquitination of spermidine/spermine N1-acetyltransferase and prevent its targeting to the proteasome for degradation
    C S Coleman
    Department of Cellular and Molecular Physiology, The Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, P O Box 850, Hershey, PA 17033, USA
    Biochem J 358:137-45. 2001
    ....
  19. ncbi request reprint Effect of S-adenosyl-1,12-diamino-3-thio-9-azadodecane, a multisubstrate adduct inhibitor of spermine synthase, on polyamine metabolism in mammalian cells
    A E Pegg
    Department of Physiology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033
    Biochemistry 28:8446-53. 1989
    ..Oxidative metabolism of the inhibitor complicates the interpretation of experiments carried out in the absence of amine oxidase inhibitors such as aminoguanidine.(ABSTRACT TRUNCATED AT 250 WORDS)..
  20. pmc Targeted overexpression of ornithine decarboxylase enhances beta-adrenergic agonist-induced cardiac hypertrophy
    L M Shantz
    Department of Cellular and Molecular Physiology H166, P O Box 850, The Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Biochem J 358:25-32. 2001
    ..Therefore these mice provide a model to study the in vivo co-operativity between high ODC activity and activation of other pathways leading to hypertrophy in the heart...
  21. ncbi request reprint Effect of N-(n-butyl)-1,3-diaminopropane on polyamine metabolism, cell growth and sensitivity to chloroethylating agents
    A E Pegg
    Department of Cellular and Molecular Physiology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033
    Biochem Pharmacol 46:717-24. 1993
    ....
  22. pmc Effect of spermine synthase deficiency on polyamine biosynthesis and content in mice and embryonic fibroblasts, and the sensitivity of fibroblasts to 1,3-bis-(2-chloroethyl)-N-nitrosourea
    C A Mackintosh
    Department of Cellular and Molecular Physiology H166, Room C4737, Pennsylvania State University College of Medicine, 500 University Drive, P O Box 850, Hershey, PA 17033, USA
    Biochem J 351:439-47. 2000
    ..Therefore both the Gy male mice and derived embryonic fibroblasts provide valuable models to study the importance of spermine and spermine synthase, without the use of inhibitors which may have additional side effects...
  23. pmc Overexpression of antizyme in the hearts of transgenic mice prevents the isoprenaline-induced increase in cardiac ornithine decarboxylase activity and polyamines, but does not prevent cardiac hypertrophy
    C A Mackintosh
    Department of Cellular and Molecular Physiology H166, Room C4737, Pennsylvania State University College of Medicine, 500 University Drive, P O Box 850, Hershey, PA 17033, USA
    Biochem J 350:645-53. 2000
    ..These transgenic mice thus provide a valuable model system in which to study the importance of polyamine levels in cardiac growth and electrophysiology in response to stress...
  24. ncbi request reprint Alteration of arginine-128 to alanine abolishes the ability of human O6-alkylguanine-DNA alkyltransferase to repair methylated DNA but has no effect on its reaction with O6-benzylguanine
    S Kanugula
    Department of Cellular and Molecular Physiology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033, USA
    Biochemistry 34:7113-9. 1995
    ..The ability of the AGT proteins to form stable complexes with DNA was therefore examined by measuring the retardation of DNA during electrophoresis.(ABSTRACT TRUNCATED AT 250 WORDS)..
  25. ncbi request reprint Reaction of O6-benzylguanine-resistant mutants of human O6-alkylguanine-DNA alkyltransferase with O6-benzylguanine in oligodeoxyribonucleotides
    A E Pegg
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, The Milton S Hershey Medical Center, Hershey, Pennsylvania 17033 0850, USA
    J Biol Chem 273:10863-7. 1998
    ..Changes in the AGT active site pocket can therefore affect the preference for repair of O6-benzyl or -methyl groups when present in an oligodeoxyribonucleotide without altering the reaction with free O6-benzylguanine...
  26. ncbi request reprint Translational regulation of ornithine decarboxylase and other enzymes of the polyamine pathway
    L M Shantz
    Department of Cellular and Molecular Physiology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 1703, USA
    Int J Biochem Cell Biol 31:107-22. 1999
    ..In contrast, the amino acid sequence that is encoded by the upstream ORF is critical for polyamine regulation of AdoMetDC synthesis and polyamines may affect synthesis by interaction with the putative peptide, MAGDIS...
  27. ncbi request reprint Mutations in human O6-alkylguanine-DNA alkyltransferase imparting resistance to O6-benzylguanine
    T M Crone
    Department of Cellular and Molecular Physiology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033
    Cancer Res 54:6221-7. 1994
    ..The development of other AGT inactivators which are still able to inactivate the resistant mutants may be necessary to maximize the potential of AGT inhibition for cancer chemotherapy...
  28. ncbi request reprint Altered spermidine/spermine N1-acetyltransferase activity as a mechanism of cellular resistance to bis(ethyl)polyamine analogues
    D E McCloskey
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 275:28708-14. 2000
    ..7Res SSAT cDNA. Expression of wtSSAT activity in C55.7Res cells restored sensitivity to bis(ethyl)polyamines. These results provided definitive evidence that SSAT activity is a critical target of the cytotoxic action of these analogues...
  29. ncbi request reprint Mechanism of the irreversible inactivation of mouse ornithine decarboxylase by alpha-difluoromethylornithine. Characterization of sequences at the inhibitor and coenzyme binding sites
    R Poulin
    Department of Cellular and Molecular Physiology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033
    J Biol Chem 267:150-8. 1992
    ..This adduct is consistent with spectral evidence showing that inactivation of the enzyme with DFMO does not entail the formation of a stable adduct between the pyridoxal 5'-phosphate, the enzyme, and the inhibitor...
  30. pmc Role of unsaturated derivatives of spermidine as substrates for spermine synthase and in supporting growth of SV-3T3 cells
    A E Pegg
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey 17033
    Biochem J 274:167-71. 1991
    ..This indicates that these compounds are substrates for the polyamine transport system, but that they are less effective than the natural polyamines in the feedback regulation of this system...
  31. ncbi request reprint Purification of human S-adenosylmethionine decarboxylase expressed in Escherichia coli and use of this protein to investigate the mechanism of inhibition by the irreversible inhibitors, 5'-deoxy-5'-[(3-hydrazinopropyl)methylamino]adenosine and 5'-([(Z)-4-
    L M Shantz
    Department of Cellular and Molecular Physiology, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033
    Biochemistry 31:6848-55. 1992
    ..These results indicate that this inhibitor leads to transamination of the pyruvate prosthetic group. Since the pyruvate is covalently linked to the protein, its replacement by alanine leads to an irreversible inactivation of AdoMetDC...
  32. ncbi request reprint Amino acid residues necessary for putrescine stimulation of human S-adenosylmethionine decarboxylase proenzyme processing and catalytic activity
    B A Stanley
    Department of Cellular and Molecular Physiology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033
    J Biol Chem 266:18502-6. 1991
    ....
  33. ncbi request reprint The role of tyrosine-158 in O6-alkylguanine-DNA alkyltransferase activity
    S Edara
    Department of Cellular and Molecular Physiology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033, USA
    Carcinogenesis 16:1637-42. 1995
    ..The hydrogen bond formed by the hydroxyl group from tyrosine-158 may also facilitate the reaction but the contribution from this interaction is relatively small...
  34. ncbi request reprint Site of pyruvate formation and processing of mammalian S-adenosylmethionine decarboxylase proenzyme
    B A Stanley
    Department of Cellular and Molecular Physiology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033
    J Biol Chem 264:21073-9. 1989
    ....
  35. ncbi request reprint Novel DNA repair alkyltransferase from Caenorhabditis elegans
    S Kanugula
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, The Milton S Hershey Medical Center, Hershey, Pennsylvania 17033 0850, USA
    Environ Mol Mutagen 38:235-43. 2001
    ..Expression of cAGT-2 in an E. coli strain lacking endogenous AGT activity provided modest but statistically significant resistance to the toxicity of N-methyl-N'-nitro-N-nitrosoguanidine, confirming that cAGT-2 is an alkyltransferase...
  36. ncbi request reprint Role of cysteine-82 in the catalytic mechanism of human S-adenosylmethionine decarboxylase
    H Xiong
    Department of Cellular and Molecular Physiology, The Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033, USA
    Biochemistry 38:2462-70. 1999
    ..On the basis of these results, it was postulated that residue Cys-82 may be the proton donor of the decarboxylation reaction catalyzed by S-adenosylmethionine decarboxylase...
  37. ncbi request reprint Mechanistic studies of the processing of human S-adenosylmethionine decarboxylase proenzyme. Isolation of an ester intermediate
    H Xiong
    Department of Cellular Physiology, The Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 274:35059-66. 1999
    ....
  38. ncbi request reprint The role of human O(6)-alkylguanine-DNA alkyltransferase in promoting 1,2-dibromoethane-induced genotoxicity in Escherichia coli
    H Liu
    Department of Cellular and Molecular Physiology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, 17033 0850, USA
    Mutat Res 452:1-10. 2000
    ..This interaction is prevented by mutations that modify the active site of AGT to exclude BG...
  39. ncbi request reprint Studies of the mechanism by which increased spermidine/spermine N1-acetyltransferase activity increases susceptibility to skin carcinogenesis
    Xiaojing Wang
    Department of Cellular and Molecular Physiology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, PO Box 850, Hershey, PA 17033, USA
    Carcinogenesis 28:2404-11. 2007
    ....
  40. pmc Spermidine/spermine-N1-acetyltransferase-2 (SSAT2) acetylates thialysine and is not involved in polyamine metabolism
    Catherine S Coleman
    Department of Cellular and Molecular Physiology, The Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, P O Box 850, Hershey, PA 17033, USA
    Biochem J 384:139-48. 2004
    ..SSAT2 should be renamed 'thialysine N(epsilon)-acetyltransferase', and may regulate this pathway...
  41. ncbi request reprint Spermine synthesis is required for normal viability, growth, and fertility in the mouse
    Xiaojing Wang
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 279:51370-5. 2004
    ..These results show that spermine synthesis is needed for normal growth, viability, and fertility in male mice and that regulation of spermine synthase content is not required...
  42. pmc Spermidine/spermine N1-acetyltransferase specifically binds to the integrin alpha9 subunit cytoplasmic domain and enhances cell migration
    Chun Chen
    Lung Biology Center, Department of Medicine, University of California San Francisco, San Francisco, CA 94110, USA
    J Cell Biol 167:161-70. 2004
    ..We conclude that SSAT directly binds to the alpha9 cytoplasmic domain and mediates alpha9-dependent enhancement of cell migration, presumably by localized effects on acetylation of polyamines or of unidentified substrates...
  43. ncbi request reprint DNAzyme-mediated silencing of ornithine decarboxylase
    Joseph M Ackermann
    Department of Pharmacology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Biochemistry 44:2143-52. 2005
    ..These results indicate that this DNAzyme may be a useful tool to study the function of ODC and may have potential therapeutic uses...
  44. ncbi request reprint Spermidine/spermine N1-acetyltransferase transient overexpression restores sensitivity of resistant human ovarian cancer cells to N1,N12-bis(ethyl)spermine and to cisplatin
    Gaetano Marverti
    Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Universita di Modena e Reggio Emilia, Via Campi 287, I 41100 Modena, Italy
    Carcinogenesis 26:1677-86. 2005
    ....
  45. ncbi request reprint Key role for p27Kip1, retinoblastoma protein Rb, and MYCN in polyamine inhibitor-induced G1 cell cycle arrest in MYCN-amplified human neuroblastoma cells
    Christopher J Wallick
    Cancer Research Center of Hawaii, University of Hawaii at Manoa, 1236 Lauhala Street, Honolulu, HI 96813, USA
    Oncogene 24:5606-18. 2005
    ..Overexpression of MYCN induces an aggressive NB phenotype with malignant behavior. We show for the first time that DFMO and SAM486A induce G1 cell cycle arrest in NB cells through p27Kip1 and Rb hypophosphorylation...
  46. pmc Overproduction of cardiac S-adenosylmethionine decarboxylase in transgenic mice
    Oleg Nisenberg
    Department of Cellular and Molecular Physiology, The Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, P O Box 850, 500 University Drive, Hershey, PA 17033, USA
    Biochem J 393:295-302. 2006
    ....
  47. pmc Structures of wild-type and mutant human spermidine/spermine N1-acetyltransferase, a potential therapeutic drug target
    Maria C Bewley
    Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA
    Proc Natl Acad Sci U S A 103:2063-8. 2006
    ..Sequence signatures group SSAT with proteins that appear to have thialysine Nepsilon-acetyltransferase activity...
  48. pmc Repair of O6-G-alkyl-O6-G interstrand cross-links by human O6-alkylguanine-DNA alkyltransferase
    Qingming Fang
    Departments of Cellular and Molecular Physiology and Pharmacology, The Pennsylvania State University College of Medicine, P O Box 850, Hershey, Pennsylvania 17033, USA
    Biochemistry 47:10892-903. 2008
    ..These results are consistent with the postulated mechanism of AGT repair that involves DNA binding and flipping of the substrate nucleotide and indicate that hAGT can repair some types of interstrand cross-link damage...
  49. pmc Interactions of human O6-alkylguanine-DNA alkyltransferase (AGT) with short single-stranded DNAs
    Joseph J Rasimas
    Department of Molecular Physiology, Penn State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 282:3357-66. 2007
    ..We hypothesize that modest binding cooperativity and high binding densities are adaptations that allow AGT to efficiently search for lesions in the context of chromatin remodeling and DNA replication...
  50. ncbi request reprint Mouse skin chemical carcinogenesis is inhibited by antizyme in promotion-sensitive and promotion-resistant genetic backgrounds
    David J Feith
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Mol Carcinog 46:453-65. 2007
    ..These studies demonstrate a tumor-suppressive effect of AZ in C57BL/6 and DBA/2 mice, and confirm the importance of ODC and polyamines in tumor development...
  51. pmc The alpha9beta1 integrin enhances cell migration by polyamine-mediated modulation of an inward-rectifier potassium channel
    Gregory W DeHart
    Lung Biology Center, Department of Medicine, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 105:7188-93. 2008
    ..These results identify a pathway through which the alpha9 integrin subunit stimulates cell migration by localized polyamine catabolism and modulation of Kir channel function...
  52. ncbi request reprint Spermidine/spermine-N(1)-acetyltransferase: a key metabolic regulator
    Anthony E Pegg
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Am J Physiol Endocrinol Metab 294:E995-1010. 2008
    ....
  53. ncbi request reprint Polyamine homeostasis in arginase knockout mice
    Joshua L Deignan
    Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 1732, USA
    Am J Physiol Cell Physiol 293:C1296-301. 2007
    ..These results suggest that endogenous arginase-derived ornithine may not directly contribute to polyamine homeostasis in mice. Alternate sources such as diet may provide sufficient polyamines for maintenance in mammalian tissues...
  54. pmc Role of MGMT in protecting against cyclophosphamide-induced toxicity in cells and animals
    Ryan J Hansen
    Committee on Cancer Biology, The University of Chicago, 5841 S Maryland Avenue, Chicago, IL 60637, USA
    DNA Repair (Amst) 6:1145-54. 2007
    ..While MGMT may be important at the cellular level, mice deficient in MGMT are not significantly more susceptible to cyclophosphamide, acrolein or CAA. Thus, our data does not support targeting MGMT to improve oxazaphosphorine therapy...
  55. pmc DNA binding, nucleotide flipping, and the helix-turn-helix motif in base repair by O6-alkylguanine-DNA alkyltransferase and its implications for cancer chemotherapy
    Julie L Tubbs
    The Scripps Research Institute, The Skaggs Institute for Chemical Biology and Department of Molecular Biology, 10550 North Torrey Pines Road, MB4, La Jolla, CA 92037, USA
    DNA Repair (Amst) 6:1100-15. 2007
    ....
  56. ncbi request reprint DNA binding and nucleotide flipping by the human DNA repair protein AGT
    Douglas S Daniels
    Skaggs Institute for Chemical Biology, The Scripps Research Institute, MB 4, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Struct Mol Biol 11:714-20. 2004
    ..Structural and biochemical results further support an unpredicted role for Tyr114 in nucleotide flipping through phosphate rotation and an efficient kinetic mechanism for locating alkylated bases...
  57. ncbi request reprint Properties of the spermidine/spermine N1-acetyltransferase mutant L156F that decreases cellular sensitivity to the polyamine analogue N1, N11-bis(ethyl)norspermine
    Diane E McCloskey
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey 17033, USA
    J Biol Chem 278:13881-7. 2003
    ..These studies indicate that the decreased cellular sensitivity to BE 3-3-3 is caused by the lack of SSAT activity induction in the presence of the analogue due to its inability to prevent the rapid degradation of the L156F-SSAT protein...
  58. ncbi request reprint 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
    Demetrius M Kokkinakis
    Department of Pathology and the Cancer Institute, The University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Clin Cancer Res 9:3801-7. 2003
    ..These results suggest that pancreatic tumors, which are resistant to DNA alkylating agents, may be sensitized to such agents when pretreated with MGMT inactivators...
  59. ncbi request reprint Caspase activation in etoposide-treated fibroblasts is correlated to ERK phosphorylation and both events are blocked by polyamine depletion
    Claudio Stefanelli
    Department of Biochemistry G Moruzzi, University of Bologna, Via Irnerio, 48, 40126, Bologna, Italy
    FEBS Lett 527:223-28. 2002
    ..These results reveal a role for polyamines in the transduction of the death signal triggered by etoposide...
  60. ncbi request reprint O6-alkylguanine-DNA alkyltransferases repair O6-methylguanine in DNA with Michaelis-Menten-like kinetics
    Aviva S Meyer
    Institute for Cancer Prevention, American Health Foundation Cancer Center, One Dana Road, Valhalla, New York 10595, USA
    Chem Res Toxicol 16:1405-9. 2003
    ..These results suggest that the sequence specificity in the repair of O(6)mG is manifested in the methyl transfer not in the O(6)mG recognition step...
  61. ncbi request reprint Paradoxical enhancement of the toxicity of 1,2-dibromoethane by O6-alkylguanine-DNA alkyltransferase
    Liping Liu
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 277:37920-8. 2002
    ..In the presence of DNA, the DNA-binding function of AGT facilitates formation of DNA adducts. In the absence of DNA, the intermediate undergoes hydrolytic decomposition to form AGT-Cys(145)-SCH(2)CH(2)OH...
  62. ncbi request reprint Monomeric S-adenosylmethionine decarboxylase from plants provides an alternative to putrescine stimulation
    Eric M Bennett
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853 1301, USA
    Biochemistry 41:14509-17. 2002
    ....
  63. pmc Active-site alkylation destabilizes human O6-alkylguanine DNA alkyltransferase
    Joseph J Rasimas
    Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Protein Sci 13:301-5. 2004
    ..5-1.2 kcal/mole and the DNA-binding function by 0.8-1.4 kcal/mole. On this basis, we propose that destabilization of the native conformational ensemble acts as a signal for ubiquitination...
  64. ncbi request reprint Repair of oligodeoxyribonucleotides by O(6)-alkylguanine-DNA alkyltransferase
    Kieu X Luu
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, The Milton S Hershey Medical Center, P O Box 850, 500 University Drive, Hershey, Pennsylvania 17033 0850, USA
    Biochemistry 41:8689-97. 2002
    ..These findings will aid in designing novel AGT inhibitors that incorporate O(6)-alkylguanine adducts in oligodeoxyribonucleotide contexts...
  65. ncbi request reprint Inactivation and degradation of O(6)-alkylguanine-DNA alkyltransferase after reaction with nitric oxide
    Liping Liu
    Department of Cellular and Molecular Physiology, The Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Cancer Res 62:3037-43. 2002
    ..This may be of particular importance because such exposure may also lead to the formation of N-nitroso compounds that can act as alkylating agents...
  66. ncbi request reprint Degradation of the alkylated form of the DNA repair protein, O(6)-alkylguanine-DNA alkyltransferase
    Meng Xu-Welliver
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, The Milton S Hershey Medical Center, Hershey, PA 17033 0850, USA
    Carcinogenesis 23:823-30. 2002
    ..This is a novel type of post-translational modification causing ubiquitination...
  67. ncbi request reprint The repair of the tobacco specific nitrosamine derived adduct O6-[4-Oxo-4-(3-pyridyl)butyl]guanine by O6-alkylguanine-DNA alkyltransferase variants
    Renée S Mijal
    Division of Environmental and Occupational Health and Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA
    Chem Res Toxicol 17:424-34. 2004
    ..In addition, differences observed in the repair of this adduct by mammalian proteins may translate into differences in sensitivity to the mutagenic and carcinogenic effects of NNK or other pyridyloxobutylating nitrosamines...
  68. ncbi request reprint Antizyme overexpression in transgenic mice reduces cell proliferation, increases apoptosis, and reduces N-nitrosomethylbenzylamine-induced forestomach carcinogenesis
    Louise Y Y Fong
    Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Cancer Res 63:3945-54. 2003
    ....
  69. ncbi request reprint Overexpression of a dominant-negative ornithine decarboxylase in mouse skin: effect on enzyme activity and papilloma formation
    Lisa M Shantz
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA
    Carcinogenesis 23:657-64. 2002
    ....
  70. pmc Characterization of transgenic mice with widespread overexpression of spermine synthase
    Yoshihiko Ikeguchi
    Department of Cellular and Molecular Physiology, The Milton S Hershey Medical Center, Pennsylvania State University College of Medicine P O Box 850, Hershey, PA 17033, USA
    Biochem J 381:701-7. 2004
    ....
  71. ncbi request reprint Targeted expression of spermidine/spermine N1-acetyltransferase increases susceptibility to chemically induced skin carcinogenesis
    Catherine S Coleman
    Department of Cellular and Molecular Physiology, The Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, PO Box 850, Hershey, PA 17033, USA
    Carcinogenesis 23:359-64. 2002
    ..These results suggest that activation of polyamine catabolism leading to increases in putrescine and N1-acetylspermidine may play a key role in chemically induced mouse skin neoplasia...
  72. ncbi request reprint Effects of zinc occupancy on human O6-alkylguanine-DNA alkyltransferase
    Joseph J Rasimas
    Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Biochemistry 42:980-90. 2003
    ..Zinc also provides conformational stability to hAGT that may influence its regulation...
  73. ncbi request reprint O6-alkylguanine-DNA alkyltransferase: low pKa and high reactivity of cysteine 145
    F Peter Guengerich
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Biochemistry 42:10965-70. 2003
    ..The high reactivity of hAGT Cys145 is postulated to be important in normal catalytic function, in cross-linking reactions involving bis-electrophiles, and in inhibition of the DNA repair function of hAGT by electrophiles...
  74. ncbi request reprint DNA-binding mechanism of O6-alkylguanine-DNA alkyltransferase. Effects of protein and DNA alkylation on complex stability
    Joseph J Rasimas
    Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey 17033, USA
    J Biol Chem 278:7973-80. 2003
    ..These results have significant implications for the mechanisms by which AGT locates and interacts with repairable alkyl lesions to effect DNA repair...
  75. ncbi request reprint Structure and mechanism of spermidine synthases
    Hong Wu
    Structural Genomics Consortium, University of Toronto, 100 College Street, Toronto, Ontario, M5G 1L5, Canada
    Biochemistry 46:8331-9. 2007
    ..The studies also provide a structural basis for the specificity of the spermidine synthase subclass of the aminopropyltransferase family...
  76. ncbi request reprint Differences in the rate of repair of O6-alkylguanines in different sequence contexts by O6-alkylguanine-DNA alkyltransferase
    Richard Coulter
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Chem Res Toxicol 20:1966-71. 2007
    ..022 to 0.000016 s(-1). The results are consistent with a mechanism in which the O6-alkylguanine can bind to AGT in either a reactive or an unreactive orientation, the proportion of which depends on the sequence context...
  77. pmc Cross-linking of the DNA repair protein Omicron6-alkylguanine DNA alkyltransferase to DNA in the presence of antitumor nitrogen mustards
    Rachel Loeber
    Department of Medicinal Chemistry and Cancer Center and Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455, USA
    Chem Res Toxicol 21:787-95. 2008
    ..Because AGT is overexpressed in many tumor types, further investigations of the potential role of AGT-DNA cross-linking in the antitumor and mutagenic activity of antitumor nitrogen mustards are warranted...
  78. ncbi request reprint Interaction of mammalian O(6)-alkylguanine-DNA alkyltransferases with O(6)-benzylguanine
    Natalia A Loktionova
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, The Milton S Hershey Medical Center, P O Box 850, 500 University Drive, Hershey, PA 17033, USA
    Biochem Pharmacol 63:1431-42. 2002
    ....
  79. pmc The crystal structure of spermidine synthase with a multisubstrate adduct inhibitor
    Sergey Korolev
    Biosciences Division and Structural Biology Center, Argonne National Laboratory, 9700 South Cass Ave, Bldg 202, Argonne, Illinois 60439, USA
    Nat Struct Biol 9:27-31. 2002
    ..The enzyme is tetrameric; each monomer consists of a C-terminal domain with a Rossmann-like fold and an N-terminal beta-stranded domain. The tetramer is assembled using a novel barrel-type oligomerization motif...
  80. ncbi request reprint Evolutionary links as revealed by the structure of Thermotoga maritima S-adenosylmethionine decarboxylase
    Angela V Toms
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    J Biol Chem 279:33837-46. 2004
    ..A homology model for the Escherichia coli AdoMetDC was generated based on the structures of the T. maritima and human AdoMetDCs...
  81. ncbi request reprint Decarboxylases involved in polyamine biosynthesis and their inactivation by nitric oxide
    Rebecca A Hillary
    Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Biochim Biophys Acta 1647:161-6. 2003
    ..The inactivation of these enzymes may mediate some of the antiproliferative actions of NO...
  82. ncbi request reprint O6-alkylguanine-DNA alkyltransferase has opposing effects in modulating the genotoxicity of dibromomethane and bromomethyl acetate
    Liping Liu
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Chem Res Toxicol 17:742-52. 2004
    ....
  83. ncbi request reprint Induction of spermidine/spermine N1-acetyltransferase in breast cancer tissues treated with the polyamine analogue N1, N11-diethylnorspermine
    Edward Gabrielson
    Department of Pathology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Bunting Blaustein Cancer Research Building, 1650 Orleans Street, Baltimore, MD 21231 1000, USA
    Cancer Chemother Pharmacol 54:122-6. 2004
    ..Therefore, to estimate the response of breast cancers to DENSpm, we measured induction of SSAT in breast cancer explants treated in vitro with this polyamine analogue...
  84. ncbi request reprint Nuclear-localizing O6-benzylguanine-resistant GFP-MGMT fusion protein as a novel in vivo selection marker
    Uimook Choi
    Laboratory of Host Defenses, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892 1886, USA
    Exp Hematol 32:709-19. 2004
    ....
  85. pmc Ornithine decarboxylase is a target for chemoprevention of basal and squamous cell carcinomas in Ptch1+/- mice
    Xiuwei Tang
    Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    J Clin Invest 113:867-75. 2004
    ..These results demonstrate the crucial importance of ODC for the induction of BCCs and indicate that chemopreventive strategies directed at inhibiting this enzyme may be useful in reducing BCCs in human populations...
  86. pmc Tissue-based assay for ornithine decarboxylase to identify patients likely to respond to difluoromethylornithine
    Victor A Levin
    Dept of Neuro Oncology, Unit 431, University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 4009, USA
    J Histochem Cytochem 52:1467-74. 2004
    ....
  87. ncbi request reprint Beta-glucuronidase-cleavable prodrugs of O6-benzylguanine and O6-benzyl-2'-deoxyguanosine
    Guangping Wei
    Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, PO Box B, Bldg 538, Frederick, Maryland 21702, USA
    J Med Chem 48:256-61. 2005
    ..These prodrugs may be useful for prodrug monotherapy of necrotic tumors that liberate beta-glucuronidase or for antibody-directed enzyme prodrug therapy with antibodies that can deliver beta-glucuronidase to target tumor cells...
  88. pmc Putrescine biosynthesis in mammalian tissues
    Catherine S Coleman
    Department of Cellular and Molecular Physiology, The Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, P O Box 850, Hershey, PA 17033, USA
    Biochem J 379:849-55. 2004
    ..Although agmatine is a known constituent of mammalian cells, it can be transported from the diet. Therefore L-ornithine decarboxylase remains the only established route for de novo putrescine biosynthesis in mammals...
  89. pmc A bifunctional DNA repair protein from Ferroplasma acidarmanus exhibits O6-alkylguanine-DNA alkyltransferase and endonuclease V activities
    Sreenivas Kanugula
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Proc Natl Acad Sci U S A 102:3617-22. 2005
    ..These results demonstrate the physiological occurrence of two completely different but functional DNA repair activities in a single polypeptide chain...
  90. ncbi request reprint Kinetic analysis of steps in the repair of damaged DNA by human O6-alkylguanine-DNA alkyltransferase
    Hong Zang
    Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    J Biol Chem 280:30873-81. 2005
    ..The results explain the overall patterns of rates of alkyl group removal versus AGT concentration and the effects of the mutations, as well as the greater affinity of AGT for DNA with O6-alkylG lesions...
  91. ncbi request reprint Characterization of a mutagenic DNA adduct formed from 1,2-dibromoethane by O6-alkylguanine-DNA alkyltransferase
    Liping Liu
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 279:4250-9. 2004
    ....
  92. ncbi request reprint X-linked spermine synthase gene (SMS) defect: the first polyamine deficiency syndrome
    A Lauren Cason
    1J C Self Research Institute, Greenwood Genetic Center, 1 Gregor Mendel Circle, Greenwood, SC 29646, USA
    Eur J Hum Genet 11:937-44. 2003
    ..Additionally, the presence of MR reflects a role for spermine in cognitive function, possibly by spermine's ability to function as an 'intrinsic gateway' molecule for inward rectifier K(+) channels...
  93. pmc Kinetics of O(6)-methyl-2'-deoxyguanosine repair by O(6)-alkylguanine DNA alkyltransferase within K-ras gene-derived DNA sequences
    Rebecca Guza
    Department of Medicinal Chemistry and The Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA
    Chem Res Toxicol 19:531-8. 2006
    ....
  94. ncbi request reprint 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
    Renée S Mijal
    Division of Environmental Health Sciences and the Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA
    Cancer Res 66:4968-74. 2006
    ..These data establish a novel functional difference between the I143V/K178R protein and other hAGTs in the repair of a toxicologically relevant substrate, O(6)-pobG...
  95. pmc Cross-linking of the human DNA repair protein O6-alkylguanine DNA alkyltransferase to DNA in the presence of 1,2,3,4-diepoxybutane
    Rachel Loeber
    University of Minnesota Cancer Center and Department of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, USA
    Chem Res Toxicol 19:645-54. 2006
    ..AGT-DNA cross-linking is a likely mechanism of DEB-mediated cytotoxicity in cells expressing this important repair protein...
  96. ncbi request reprint Function of domains of human O6-alkylguanine-DNA alkyltransferase
    Qingming Fang
    Department of Cellular and Molecular Physiology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Biochemistry 44:15396-405. 2005
    ..The N-terminal domain was also able to produce moderate protection from MNNG when expressed in E. coli. This cryptic Zn2+-dependent DNA repair activity may be relevant to the evolution and function of AGTs...

Research Grants70

  1. INVESTIGATIONS OF MAMMALIAN AMINOPROPYLTRANSFERASES
    ANTHONY PEGG; Fiscal Year: 2002
    ..A similar protocol to that used to obtain the BE-3-3-3 resistant cells will be used to isolate cells resistant to CHE-Spm which will then be used to study its mechanism of action. ..
  2. ALKYLTRANSFERASE INHIBITORS FOR CANCER CHEMOTHERAPY
    ANTHONY PEGG; Fiscal Year: 2004
    ....
  3. ALKYLTRANSFERASE INHIBITORS FOR CANCER CHEMOTHERAPY
    ANTHONY PEGG; Fiscal Year: 2007
    ..These experiments provide a means to reverse a well know source of resistance to alkylating agents that are used in such therapy. As such, they will increase the likelihood that these agents will produce therapeutic responses. ..
  4. Persistence of Alkylated DNA Carcinogenesis
    ANTHONY PEGG; Fiscal Year: 2002
    ..5) To characterize and evaluate the biological significance of the differences in hAGT activity imparted by different polymorphic forms of the protein. ..
  5. ALKYLTRANSFERASE INHIBITORS FOR CANCER CHEMOTHERAPY
    ANTHONY PEGG; Fiscal Year: 2008
    ..These experiments provide a means to reverse a well know source of resistance to alkylating agents that are used in such therapy. As such, they will increase the likelihood that these agents will produce therapeutic responses. ..
  6. PERSISTENCE OF ALKYLATED DNA IN CARCINOGENESIS
    ANTHONY PEGG; Fiscal Year: 2000
    ..Cells transfected with AGT, AGT mutants that may affect nuclear localization and with Ada-C will be examined for distribution of AGT and for protection from alkylating agents. ..
  7. ALKYLTRANSFERASE INHIBITORS FOR CANCER CHEMOTHERAPY
    ANTHONY PEGG; Fiscal Year: 2003
    ....
  8. ALKYLTRANSFERASE INHIBITORS FOR CANCER CHEMOTHERAPY
    ANTHONY PEGG; Fiscal Year: 2002
    ....
  9. INVESTIGATIONS OF MAMMALIAN AMINOPROPYLTRANSFERASES
    ANTHONY PEGG; Fiscal Year: 2003
    ..A similar protocol to that used to obtain the BE-3-3-3 resistant cells will be used to isolate cells resistant to CHE-Spm which will then be used to study its mechanism of action. ..
  10. Persistence of Alkylated DNA Carcinogenesis
    ANTHONY PEGG; Fiscal Year: 2003
    ..5) To characterize and evaluate the biological significance of the differences in hAGT activity imparted by different polymorphic forms of the protein. ..
  11. PERSISTENCE OF ALKYLATED DNA IN CARCINOGENESIS
    ANTHONY PEGG; Fiscal Year: 2001
    ..Cells transfected with AGT, AGT mutants that may affect nuclear localization and with Ada-C will be examined for distribution of AGT and for protection from alkylating agents. ..
  12. INVESTIGATIONS OF MAMMALIAN AMINOPROPYLTRANSFERASES
    ANTHONY PEGG; Fiscal Year: 2001
    ..A similar protocol to that used to obtain the BE-3-3-3 resistant cells will be used to isolate cells resistant to CHE-Spm which will then be used to study its mechanism of action. ..
  13. MAMMALIAN AMINOPROPYLTRANSFERASES
    ANTHONY PEGG; Fiscal Year: 2000
    ..They will also aid in the design of therapeutically useful polyamine antimetabolites and in the adoption of effective protocols using currently available agents. ..
  14. ALKYLTRANSFERASE INHIBITORS FOR CANCER CHEMOTHERAPY
    ANTHONY PEGG; Fiscal Year: 2001
    ....
  15. ALKYLTRANSFERASE INHIBITORS FOR CANCER CHEMOTHERAPY
    ANTHONY PEGG; Fiscal Year: 2000
    ....
  16. MAMMALIAN AMINOPROPYLTRANSFERASES
    ANTHONY PEGG; Fiscal Year: 1999
    ..They will also aid in the design of therapeutically useful polyamine antimetabolites and in the adoption of effective protocols using currently available agents. ..
  17. Persistence of Alkylated DNA Carcinogenesis
    ANTHONY PEGG; Fiscal Year: 2004
    ..5) To characterize and evaluate the biological significance of the differences in hAGT activity imparted by different polymorphic forms of the protein. ..
  18. INVESTIGATIONS OF MAMMALIAN AMINOPROPYLTRANSFERASES
    ANTHONY PEGG; Fiscal Year: 2004
    ..A similar protocol to that used to obtain the BE-3-3-3 resistant cells will be used to isolate cells resistant to CHE-Spm which will then be used to study its mechanism of action. ..
  19. INVESTIGATIONS OF MAMMALIAN AMINOPROPYLTRANSFERASES
    ANTHONY PEGG; Fiscal Year: 2009
    ..abstract_text> ..
  20. ALKYLTRANSFERASE INHIBITORS FOR CANCER CHEMOTHERAPY
    ANTHONY PEGG; Fiscal Year: 2009
    ..These experiments provide a means to reverse a well know source of resistance to alkylating agents that are used in such therapy. As such, they will increase the likelihood that these agents will produce therapeutic responses. ..
  21. INVESTIGATIONS OF MAMMALIAN AMINOPROPYLTRANSFERASES
    ANTHONY PEGG; Fiscal Year: 2008
    ..abstract_text> ..
  22. Persistence of Alkylated DNA Carcinogenesis
    ANTHONY PEGG; Fiscal Year: 2008
    ..These experiments will aid in the understanding of the individual risks associated with exposure to alkylating agents and an important class of environmental carcinogens. ..
  23. MAMMALIAN POLYAMINE METABOLISM
    ANTHONY PEGG; Fiscal Year: 2008
    ..The knowledge generated in this research will aid in the prevention and treatment of cancer. ..
  24. INVESTIGATIONS OF MAMMALIAN AMINOPROPYLTRANSFERASES
    ANTHONY PEGG; Fiscal Year: 2007
    ..abstract_text> ..
  25. ALKYLTRANSFERASE INHIBITORS FOR CANCER CHEMOTHERAPY
    ANTHONY PEGG; Fiscal Year: 2006
    ..These experiments provide a means to reverse a well know source of resistance to alkylating agents that are used in such therapy. As such, they will increase the likelihood that these agents will produce therapeutic responses. ..
  26. MAMMALIAN POLYAMINE METABOLISM
    ANTHONY PEGG; Fiscal Year: 2007
    ..The knowledge generated in this research will aid in the prevention and treatment of cancer. [unreadable] [unreadable]..
  27. Persistence of Alkylated DNA Carcinogenesis
    ANTHONY PEGG; Fiscal Year: 2007
    ..These experiments will aid in the understanding of the individual risks associated with exposure to alkylating agents and an important class of environmental carcinogens. [unreadable] [unreadable] [unreadable] [unreadable]..
  28. INVESTIGATIONS OF MAMMALIAN AMINOPROPYLTRANSFERASES
    ANTHONY PEGG; Fiscal Year: 2006
    ..abstract_text> ..
  29. MAMMALIAN POLYAMINE METABOLISM
    ANTHONY PEGG; Fiscal Year: 2006
    ..The knowledge generated in this research will aid in the prevention and treatment of cancer. [unreadable] [unreadable]..
  30. Persistence of Alkylated DNA Carcinogenesis
    ANTHONY PEGG; Fiscal Year: 2006
    ..5) To characterize and evaluate the biological significance of the differences in hAGT activity imparted by different polymorphic forms of the protein. ..
  31. INVESTIGATIONS OF MAMMALIAN AMINOPROPYLTRANSFERASES
    ANTHONY PEGG; Fiscal Year: 2005
    ..abstract_text> ..
  32. ALKYLTRANSFERASE INHIBITORS FOR CANCER CHEMOTHERAPY
    ANTHONY PEGG; Fiscal Year: 2005
    ....
  33. Persistence of Alkylated DNA Carcinogenesis
    ANTHONY PEGG; Fiscal Year: 2005
    ..5) To characterize and evaluate the biological significance of the differences in hAGT activity imparted by different polymorphic forms of the protein. ..
  34. ALKYLTRANSFERASE INHIBITORS FOR CANCER CHEMOTHERAPY
    ANTHONY PEGG; Fiscal Year: 1999
    ....
  35. PERSISTENCE OF ALKYLATED DNA IN CARCINOGENESIS
    ANTHONY PEGG; Fiscal Year: 1999
    ..Cells transfected with AGT, AGT mutants that may affect nuclear localization and with Ada-C will be examined for distribution of AGT and for protection from alkylating agents. ..
  36. INVESTIGATIONS OF MAMMALIAN AMINOPROPYLTRANSFERASES
    ANTHONY PEGG; Fiscal Year: 1992
    ..These studies will identify compounds and protocols to maximize the effectiveness of antitumor strategies which perturb cellular polyamine content...
  37. INVESTIGATIONS OF MAMMALIAN AMINOPROPYLTRANSFERASES
    ANTHONY PEGG; Fiscal Year: 1980
    ....
  38. PERSISTENCE OF ALKYLATED DNA IN CARCINOGENESIS
    ANTHONY PEGG; Fiscal Year: 1980
    ..The enzyme responsible for the removal of O6-methylguanine from rat liver has been partially purified and the properties of this enzyme are currently under investigation...
  39. INVESTIGATIONS OF MAMMALIAN AMINOPROPYLTRANSFERASES
    ANTHONY PEGG; Fiscal Year: 1991
    ..8-Azido derivatives of decarboxylated AdoMet and MTA have been synthesized and will be used as photoactivatable probes for spermidine synthase, spermine synthase and MTA phosphorylase...
  40. INVESTIGATIONS OF MAMMALIAN AMINOPROPYLTRANSFERASES
    ANTHONY PEGG; Fiscal Year: 1990
    ..8-Azido derivatives of decarboxylated AdoMet and MTA have been synthesized and will be used as photoactivatable probes for spermidine synthase, spermine synthase and MTA phosphorylase...