alkylation

Summary

Summary: The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group.

Top Publications

  1. ncbi Alkylation damage in DNA and RNA--repair mechanisms and medical significance
    Finn Drabløs
    Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, N 7489 Trondheim, Norway
    DNA Repair (Amst) 3:1389-407. 2004
  2. doi Selective alkylation of beta(II)-tubulin and thioredoxin-1 by structurally related subsets of aryl chloroethylureas leading to either anti-microtubules or redox modulating agents
    Jessica S Fortin
    Unité des Biotechnologies et de Bioingénierie, CHUQ, Hopital Saint Francois d Assise, Quebec, QC, Canada G1L 3L5
    Bioorg Med Chem 16:7277-90. 2008
  3. doi Ranking the susceptibility of disulfide bonds in human IgG1 antibodies by reduction, differential alkylation, and LC-MS analysis
    Hongcheng Liu
    Process Sciences Department, 100 Research Drive, Abbott Bioresearch Center, Worcester, Massachusetts 01605, USA
    Anal Chem 82:5219-26. 2010
  4. pmc Chemical biology of mutagenesis and DNA repair: cellular responses to DNA alkylation
    Nidhi Shrivastav
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Carcinogenesis 31:59-70. 2010
  5. pmc Auxiliary-assisted palladium-catalyzed arylation and alkylation of sp2 and sp3 carbon-hydrogen bonds
    Dmitry Shabashov
    Department of Chemistry, University of Houston, Houston, Texas 77204 5003, USA
    J Am Chem Soc 132:3965-72. 2010
  6. doi Picomole-level mapping of protein disulfides by mass spectrometry following partial reduction and alkylation
    Susan F Foley
    Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142, USA
    Anal Biochem 377:95-104. 2008
  7. pmc Engineering the DNA cytosine-5 methyltransferase reaction for sequence-specific labeling of DNA
    Grazvydas Lukinavicius
    Department of Biological DNA Modification, Institute of Biotechnology, Vilnius University, 02241 Vilnius, Lithuania
    Nucleic Acids Res 40:11594-602. 2012
  8. pmc Slx4 becomes phosphorylated after DNA damage in a Mec1/Tel1-dependent manner and is required for repair of DNA alkylation damage
    Sonja Flott
    MRC Protein Phosphorylation Unit, Medical Sciences Institute Wellcome Trust Biocentre Complex, Dow St, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Biochem J 391:325-33. 2005
  9. pmc DNA unwinding by ASCC3 helicase is coupled to ALKBH3-dependent DNA alkylation repair and cancer cell proliferation
    Sebastian Dango
    Division of Newborn Medicine and Epigenetics Program, Department of Medicine, Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 44:373-84. 2011
  10. pmc Reduction-alkylation strategies for the modification of specific monoclonal antibody disulfides
    Michael M C Sun
    Seattle Genetics, Inc, 21823 30th Drive SE, Bothell, Washington 98021, USA
    Bioconjug Chem 16:1282-90. 2005

Detail Information

Publications392 found, 100 shown here

  1. ncbi Alkylation damage in DNA and RNA--repair mechanisms and medical significance
    Finn Drabløs
    Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, N 7489 Trondheim, Norway
    DNA Repair (Amst) 3:1389-407. 2004
    b>Alkylation lesions in DNA and RNA result from endogenous compounds, environmental agents and alkylating drugs. Simple methylating agents, e.g...
  2. doi Selective alkylation of beta(II)-tubulin and thioredoxin-1 by structurally related subsets of aryl chloroethylureas leading to either anti-microtubules or redox modulating agents
    Jessica S Fortin
    Unité des Biotechnologies et de Bioingénierie, CHUQ, Hopital Saint Francois d Assise, Quebec, QC, Canada G1L 3L5
    Bioorg Med Chem 16:7277-90. 2008
    ....
  3. doi Ranking the susceptibility of disulfide bonds in human IgG1 antibodies by reduction, differential alkylation, and LC-MS analysis
    Hongcheng Liu
    Process Sciences Department, 100 Research Drive, Abbott Bioresearch Center, Worcester, Massachusetts 01605, USA
    Anal Chem 82:5219-26. 2010
    ..A method including reduction, differential alkylation, and liquid chromatography-mass spectrometry (LC-MS) analysis was developed and employed to investigate the ..
  4. pmc Chemical biology of mutagenesis and DNA repair: cellular responses to DNA alkylation
    Nidhi Shrivastav
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Carcinogenesis 31:59-70. 2010
    ..Here, we describe the respective contributions of specific DNA lesions to the biological effects of low molecular weight alkylating agents...
  5. pmc Auxiliary-assisted palladium-catalyzed arylation and alkylation of sp2 and sp3 carbon-hydrogen bonds
    Dmitry Shabashov
    Department of Chemistry, University of Houston, Houston, Texas 77204 5003, USA
    J Am Chem Soc 132:3965-72. 2010
    We have developed a method for auxiliary-directed, palladium-catalyzed beta-arylation and alkylation of sp(3) and sp(2) C-H bonds in carboxylic acid derivatives...
  6. doi Picomole-level mapping of protein disulfides by mass spectrometry following partial reduction and alkylation
    Susan F Foley
    Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142, USA
    Anal Biochem 377:95-104. 2008
    ..5 nmol), in two cysteine-rich polypeptide domains using a new strategy involving partial reduction/alkylation of the protein, followed by peptide mapping and tanden mass spectrometry (MS/MS) sequencing on a nanoflow liquid ..
  7. pmc Engineering the DNA cytosine-5 methyltransferase reaction for sequence-specific labeling of DNA
    Grazvydas Lukinavicius
    Department of Biological DNA Modification, Institute of Biotechnology, Vilnius University, 02241 Vilnius, Lithuania
    Nucleic Acids Res 40:11594-602. 2012
    ....
  8. pmc Slx4 becomes phosphorylated after DNA damage in a Mec1/Tel1-dependent manner and is required for repair of DNA alkylation damage
    Sonja Flott
    MRC Protein Phosphorylation Unit, Medical Sciences Institute Wellcome Trust Biocentre Complex, Dow St, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Biochem J 391:325-33. 2005
    ..cleave replication fork-like structures in vitro, and cells lacking SLX4 are hypersensitive to DNA alkylation damage. Here we report that Slx4 becomes phosphorylated in cells exposed to a wide range of genotoxins...
  9. pmc DNA unwinding by ASCC3 helicase is coupled to ALKBH3-dependent DNA alkylation repair and cancer cell proliferation
    Sebastian Dango
    Division of Newborn Medicine and Epigenetics Program, Department of Medicine, Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 44:373-84. 2011
    ..ALKBH3 is overexpressed in various cancers, and both ALKBH3 and ASCC are important for alkylation damage resistance in these tumor cell lines...
  10. pmc Reduction-alkylation strategies for the modification of specific monoclonal antibody disulfides
    Michael M C Sun
    Seattle Genetics, Inc, 21823 30th Drive SE, Bothell, Washington 98021, USA
    Bioconjug Chem 16:1282-90. 2005
    ..b>Alkylation of the resulting cAC10 cysteine thiols with the potent antimitotic agent monomethyl auristatin E (MMAE) enabled ..
  11. ncbi Crystal structure of a human alkylbase-DNA repair enzyme complexed to DNA: mechanisms for nucleotide flipping and base excision
    A Y Lau
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 95:249-58. 1998
    ..DNA glycosylase removes a diverse group of damaged bases from DNA, including cytotoxic and mutagenic alkylation adducts of purines...
  12. pmc Carnosic acid, a catechol-type electrophilic compound, protects neurons both in vitro and in vivo through activation of the Keap1/Nrf2 pathway via S-alkylation of targeted cysteines on Keap1
    Takumi Satoh
    Department of Welfare Engineering, Faculty of Engineering, Iwate University, Morioka, Iwate, Japan
    J Neurochem 104:1116-31. 2008
    ..electrophilic carbon centers that react with specific cysteine residues on targeted proteins via thiol (S-)alkylation. Although plants produce a variety of physiologically active electrophilic compounds, the detailed mechanism of ..
  13. ncbi Cesium effect: high chemoselectivity in direct N-alkylation of amines
    Ralph Nicholas Salvatore
    Department of Chemistry, University of South Florida, 4202 East Fowler Avenue, Tampa, Florida 33620 5250, USA
    J Org Chem 67:674-83. 2002
    A novel method for the mono-N-alkylation of primary amines, diamines, and polyamines was developed using cesium bases in order to prepare secondary amines efficiently...
  14. doi 2-O-alkylated para-benzamide α-helix mimetics: the role of scaffold curvature
    Valeria Azzarito
    School of Chemistry, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, United Kingdom
    Org Biomol Chem 10:6469-72. 2012
    ..Comparison with regioisomeric 3-O-alkylated benzamides permits a preliminary evaluation of the role that mimetic curvature has in determining molecular recognition properties...
  15. ncbi AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli
    Pål Ø Falnes
    Centre for Molecular Biology and Neuroscience, and Institute of Medical Microbiology, University of Oslo, National Hospital, 0027 Oslo, Norway
    Nature 419:178-82. 2002
    The bacterial AlkB protein is known to be involved in cellular recovery from alkylation damage; however, the function of this protein remains unknown...
  16. doi N-alkylated oligoamide alpha-helical proteomimetics
    Frederick Campbell
    School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, United Kingdom
    Org Biomol Chem 8:2344-51. 2010
    ..The utility of these scaffolds as proteomimetics is exemplified through the identification of potent microM inhibitors of the p53-hDM2 helix mediated PPI--a key oncogenic target...
  17. ncbi DNA sequence- and structure-selective alkylation of guanine N2 in the DNA minor groove by ecteinascidin 743, a potent antitumor compound from the Caribbean tunicate Ecteinascidia turbinata
    Y Pommier
    Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 4255, USA
    Biochemistry 35:13303-9. 1996
    ..These data indicate that ecteinascidin 743 is a novel DNA minor groove, guanine-specific alkylating agent...
  18. doi Stereoselective synthesis of β-alkylated α-amino acids via palladium-catalyzed alkylation of unactivated methylene C(sp3)-H bonds with primary alkyl halides
    Shu Yu Zhang
    Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, USA
    J Am Chem Soc 135:12135-41. 2013
    We report a new set of reactions based on the Pd-catalyzed alkylation of methylene C(sp(3))-H bonds of aliphatic quinolyl carboxamides with α-haloacetate and methyl iodide and applications in the stereoselective synthesis of various β-..
  19. pmc Tyrosyl-DNA phosphodiesterase 1 (TDP1) repairs DNA damage induced by topoisomerases I and II and base alkylation in vertebrate cells
    Junko Murai
    Department of Radiation Genetics, Kyoto University Graduate School of Medicine, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
    J Biol Chem 287:12848-57. 2012
    ..Together, our findings reveal a broad involvement of Tdp1 in DNA repair and clarify the role of human TDP1 in the repair of Top2-induced DNA damage...
  20. pmc A directed evolution design of a GCG-specific DNA hemimethylase
    Ruta Gerasimaite
    Laboratory of Biological DNA Modification, Institute of Biotechnology, Graiciuno 8, LT 02241 Vilnius, Lithuania
    Nucleic Acids Res 37:7332-41. 2009
    ..The designed C5-MTase can be used to produce hemimethylated CpG sites in DNA, which are valuable substrates for studies of mammalian maintenance MTases...
  21. pmc Off-target thiol alkylation by the NADPH oxidase inhibitor 3-benzyl-7-(2-benzoxazolyl)thio-1,2,3-triazolo[4,5-d]pyrimidine (VAS2870)
    Qi An Sun
    Institute for Transformative Molecular Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
    Free Radic Biol Med 52:1897-902. 2012
    ..RyR1 exposed in situ to VAS2870 and of VAS2870-treated glutathione indicated that thiol modification is through alkylation by the benzyltriazolopyrimidine moiety of VAS2870...
  22. pmc In vitro selection of a novel catalytic RNA: characterization of a sulfur alkylation reaction and interaction with a small peptide
    M Wecker
    Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder 80304, USA
    RNA 2:982-94. 1996
    ..This hairpin structure is also implicated in the recognition of the peptide substrate...
  23. pmc The tobacco smoke component, acrolein, suppresses innate macrophage responses by direct alkylation of c-Jun N-terminal kinase
    Milena Hristova
    Department of Pathology, College of Medicine, University of Vermont, Burlington, 05405, USA
    Am J Respir Cell Mol Biol 46:23-33. 2012
    ..p50, as well as JNK2, a critical mediator of innate macrophage responses, were revealed as direct targets for alkylation by acrolein...
  24. ncbi Modification of cysteine residues by alkylation. A tool in peptide mapping and protein identification
    S Sechi
    The Rockefeller University, New York, New York 10021, USA
    Anal Chem 70:5150-8. 1998
    ..Here we show that cysteine alkylation is required to ensure maximal coverage in matrix-assisted laser desorption/ionization time-of-flight mass ..
  25. pmc Stabilization of mutant p53 via alkylation of cysteines and effects on DNA binding
    Joel L Kaar
    Medical Research Council Centre for Protein Engineering, Cambridge CB2 0QH, United Kingdom
    Protein Sci 19:2267-78. 2010
    ..We found that the modifications progressively reduced DNA-binding activity of full-length p53. In light of these results, it is likely that the anticancer activity of the alkylating drugs works via a nontranscriptional activity of p53...
  26. doi 2-hydroxyisoquinoline-1,3(2H,4H)-diones as inhibitors of HIV-1 integrase and reverse transcriptase RNase H domain: influence of the alkylation of position 4
    Muriel Billamboz
    Universite Lille Nord de France, F 59000 Lille, France
    Eur J Med Chem 46:535-46. 2011
    ..However these identified integrase inhibitors provide a very good basis for the development of new hits...
  27. pmc A systematic investigation of quaternary ammonium ions as asymmetric phase-transfer catalysts. Application of quantitative structure activity/selectivity relationships
    Scott E Denmark
    Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, Illinois 61801, United States
    J Org Chem 76:4337-57. 2011
    ..of quantitative structure-activity relationships (QSAR) and -selectivity relationships (QSSR) for the alkylation of a protected glycine imine with libraries of quaternary ammonium ion catalysts...
  28. doi Synergistic cytotoxicity of N-methyl-N'-nitro-N-nitrosoguanidine and absence of poly(ADP-ribose) glycohydrolase involves chromatin decondensation
    Yiran Zhou
    Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, WA 99164, USA
    Int J Oncol 39:121-7. 2011
    ..glycohydrolase (PARG), which leads to the inhibition of PAR hydrolysis, would lead to increased DNA alkylation after treatment with low doses of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)...
  29. pmc Activity and regulation of archaeal DNA alkyltransferase: conserved protein involved in repair of DNA alkylation damage
    Giuseppe Perugino
    Institute of Protein Biochemistry, Consiglio Nazionale delle Ricerche, Via P Castellino 111, 80131 Naples, Italy
    J Biol Chem 287:4222-31. 2012
    ..in eucarya, bacteria and archaea, acting by a unique reaction mechanism, which leads to direct repair of DNA alkylation damage and irreversible protein alkylation...
  30. pmc Increased PARP-1 association with DNA in alkylation damaged, PARP-inhibited mouse fibroblasts
    Padmini S Kedar
    Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, 111 T W Alexander Drive, Research Triangle Park, NC 27709, USA
    Mol Cancer Res 10:360-8. 2012
    ..designed to evaluate the prediction that inhibited PARP-1 remains DNA associated in cells undergoing repair of alkylation-induced damage...
  31. doi Activation of the Nrf2/ARE pathway via S-alkylation of cysteine 151 in the chemopreventive agent-sensor Keap1 protein by falcarindiol, a conjugated diacetylene compound
    Tomokazu Ohnuma
    Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432 1 Horinouchi, Hachioji shi, Tokyo 192 0392, Japan
    Toxicol Appl Pharmacol 244:27-36. 2010
    ..Our results demonstrate that falcarindiol having conjugated diacetylene carbons covalently modifies the Cys151 residue in Keap1 and that the inactivation of Keap1 by falcarindiol leads to activation of the Nrf2/ARE pathway...
  32. pmc A general strategy for target-promoted alkylation in biological systems
    Qibing Zhou
    Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA
    Proc Natl Acad Sci U S A 100:15452-7. 2003
    Selective alkylation of a chosen sequence of DNA typically relies on ligand-directed delivery of a compound that expresses an intrinsic reactivity...
  33. doi Quantitative proteomics and dynamic imaging reveal that G3BP-mediated stress granule assembly is poly(ADP-ribose)-dependent following exposure to MNNG-induced DNA alkylation
    Maxim Isabelle
    Centre de recherche du CHUQ, Laval University, Cancer Department, Quebec, Canada
    J Cell Sci 125:4555-66. 2012
    ..in stress granule formation, notably the ras-GAP SH3-binding protein G3BP, as well as in the later phases of alkylation-stress-induced responses...
  34. pmc Sites of alkylation of human Keap1 by natural chemoprevention agents
    Yan Luo
    Department of Medicinal Chemistry and Pharmacognosy, University of Illinois College of Pharmacy, Chicago, Illinois, USA
    J Am Soc Mass Spectrom 18:2226-32. 2007
    ..b>Alkylation of one or more of the 27 cysteine sulfhydryl groups of human Keap1 is proposed to lead to Nrf2 nuclear ..
  35. pmc Schizosaccharomyces pombe Swi1, Swi3, and Hsk1 are components of a novel S-phase response pathway to alkylation damage
    Elena Sommariva
    Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 0TL, United Kingdom
    Mol Cell Biol 25:2770-84. 2005
    ..In conclusion, Swi1, Swi3, and Hsk1 act in a novel S-phase checkpoint pathway that contributes to replication fork maintenance and to survival of alkylation damage.
  36. pmc S-Adenosylmethionine-dependent alkylation reactions: when are radical reactions used?
    Hening Lin
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14850, United States
    Bioorg Chem 39:161-70. 2011
    ..reaction mechanisms? Here I aim to rationalize the choice of different reaction mechanisms in SAM-dependent alkylation reaction by analyzing a few enzymatic reactions in depth...
  37. pmc The detection of alkylation damage in the DNA of human gastrointestinal tissues
    C N Hall
    Department of Surgery, Wythenshawe Hospital, Manchester
    Br J Cancer 64:59-63. 1991
    ..300 mu moles mole-1 adenine was heterogeneously distributed both between and within individuals. The pattern of alkylation of tissue DNA appears to differ when comparison is made between gastric and colorectal samples...
  38. ncbi Roles of MGMT and MLH1 proteins in alkylation-induced apoptosis and mutagenesis
    Yasumitsu Takagi
    Frontier Research Center, Fukuoka Dental College, Fukuoka 814 0193, Japan
    DNA Repair (Amst) 2:1135-46. 2003
    To examine involvement of mismatch repair system in alkylation-induced apoptosis and mutagenesis, cell lines defective in the Mgmt gene encoding a DNA repair enzyme, O(6)-methylguanine-DNA methyltransferase, and/or the Mlh1 gene encoding ..
  39. ncbi Reduction and alkylation of proteins in preparation of two-dimensional map analysis: why, when, and how?
    B Herbert
    Proteome Systems, North Ryde, Sydney, NSW, Australia
    Electrophoresis 22:2046-57. 2001
    ..prior to the isoelectric focusing/immobilized pH gradient (IEF/IPG) step, followed by a second reduction/alkylation step in between the first and second dimension, in preparation for the sodium dodecyl sulfate-polyacrylamide gel ..
  40. ncbi Enantioselective synthesis of 3,3-disubstituted piperidine derivatives by enolate dialkylation of phenylglycinol-derived oxazolopiperidone lactams
    Mercedes Amat
    Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain
    J Org Chem 72:4431-9. 2007
    ..The usefulness of the methodology is illustrated by the conversion of some of the dialkylated lactams into known synthetic precursors of alkaloids and by the total synthesis of (-)-quebrachamine...
  41. pmc Active site and complete sequence of the suicidal methyltransferase that counters alkylation mutagenesis
    B Demple
    Proc Natl Acad Sci U S A 82:2688-92. 1985
    The inducible resistance to alkylation mutagenesis and killing in Escherichia coli (the adaptive response) is controlled by the ada gene...
  42. pmc Alkylation of prohibitin by cyclohexylphenyl-chloroethyl urea on an aspartyl residue is associated with cell cycle G(1) arrest in B16 cells
    B Bouchon
    University Clermont 1, UFR Pharmacie, Clermont Ferrand, France
    Br J Pharmacol 152:449-55. 2007
    ..We hypothesised that these observations were linked to a differential protein alkylation pattern.
  43. pmc Serendipitous alkylation of a Plk1 ligand uncovers a new binding channel
    Fa Liu
    Chemical Biology Laboratory, Molecular Discovery Program, Center for Cancer Research, National Cancer Institute Frederick, Frederick, Maryland, USA
    Nat Chem Biol 7:595-601. 2011
    We obtained unanticipated synthetic byproducts from alkylation of the δ(1) nitrogen (N3) of the histidine imidazole ring of the polo-like kinase-1 (Plk1) polo-box domain (PBD)-binding peptide PLHSpT...
  44. ncbi A simplified procedure for the reduction and alkylation of cysteine residues in proteins prior to proteolytic digestion and mass spectral analysis
    John E Hale
    Enabling Biology Division, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
    Anal Biochem 333:174-81. 2004
    A procedure for reduction and alkylation of cysteine residues in proteins was developed using the volatile reagents triethylphosphine and iodoethanol...
  45. ncbi 3-Methyladenine DNA glycosylase-deficient Aag null mice display unexpected bone marrow alkylation resistance
    Richard B Roth
    Division of Bioengineering and Environmental Health, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Cancer Res 62:656-60. 2002
    ..Moreover, an alkylation-resistant phenotype was observed in vivo using the BM micronucleus assay as a measure of chromosome damage...
  46. ncbi Repair and genetic consequences of endogenous DNA base damage in mammalian cells
    Deborah E Barnes
    Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
    Annu Rev Genet 38:445-76. 2004
    ..The genetic instability characteristic of cancer cells may be due, in part, to mutations in genes whose products normally function to ensure DNA integrity...
  47. ncbi Sequencing and mass profiling highly modified conotoxins using global reduction/alkylation followed by mass spectrometry
    Jennifer A Jakubowski
    Department of Chemistry and the Beckman Institute, University of Illinois, Urbana, Illinois 61801, USA
    Anal Chem 76:6541-7. 2004
    ..Comparison of the mass profiles of peptides and CID spectra before and after the global reduction and alkylation enables cysteine-containing conopeptides to be ascertained...
  48. ncbi Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA
    Per Arne Aas
    Institute of Cancer Research and Molecular Biology, Norwegian University of Science and Technology, N 7489 Trondheim, Norway
    Nature 421:859-63. 2003
    ..b>Alkylation damage in DNA is repaired by at least three different mechanisms, including damage reversal by oxidative ..
  49. pmc Alkylation of the tumor suppressor PTEN activates Akt and β-catenin signaling: a mechanism linking inflammation and oxidative stress with cancer
    Tracy M Covey
    Department of Medicinal Chemistry, University of Utah Health Sciences Center, Salt Lake City, Utah, United States of America
    PLoS ONE 5:e13545. 2010
    ..b>Alkylation of PTEN by α,β-enals/enones and interference with its restraint of cellular PKB/Akt signaling may accentuate ..
  50. pmc Preferential DNA damage prevention by the E. coli AidB gene: A new mechanism for the protection of specific genes
    Valentina Rippa
    Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655, USA
    DNA Repair (Amst) 10:934-41. 2011
    ..The DNA binding domain is required to target AidB to specific genes preferentially protecting them from alkylation damage...
  51. pmc Sequential activation of poly(ADP-ribose) polymerase 1, calpains, and Bax is essential in apoptosis-inducing factor-mediated programmed necrosis
    Rana S Moubarak
    Apoptose et Systeme Immunitaire, CNRS URA 1961, Institut Pasteur, 25 rue du Dr Roux, 75015 Paris, France
    Mol Cell Biol 27:4844-62. 2007
    ..Our data shed new light on the mechanisms regulating AIF-dependent necrosis and support the notion that, like apoptosis, necrosis could be a highly regulated cell death program...
  52. doi The roles of poly(ADP-ribose)-metabolizing enzymes in alkylation-induced cell death
    O Cohausz
    Institute of Pharmacology and Toxicology, University of Zurich Vetsuisse, Winterthurerstrasse 260, 8057, Zurich, Switzerland
    Cell Mol Life Sci 65:644-55. 2008
    ..We found that PARP-1, but not PARP-2 and PARG, contributed to alkylation-induced cell death. Likewise, AIF translocation was only affected by PARP-1...
  53. ncbi BER, MGMT, and MMR in defense against alkylation-induced genotoxicity and apoptosis
    B Kaina
    Division of Applied Toxicology, Institute of Toxicology, University of Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz, Germany
    Prog Nucleic Acid Res Mol Biol 68:41-54. 2001
    ..Obviously, nonrepaired BER intermediates are clastogenic and act as a strong trigger of the apoptotic pathway. The elements of this pathway are currently under investigation...
  54. pmc Parp1 activation in mouse embryonic fibroblasts promotes Pol beta-dependent cellular hypersensitivity to alkylation damage
    Elena Jelezcova
    Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, PA 15213, USA
    Mutat Res 686:57-67. 2010
    ..Parp1 may therefore function in BER as a tumor suppressor by initiating cell death and preventing the accumulation of cells with chromosomal damage due to a BER defect...
  55. pmc Alkylation DNA damage in combination with PARP inhibition results in formation of S-phase-dependent double-strand breaks
    Michelle L Heacock
    Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, NC 27709, USA
    DNA Repair (Amst) 9:929-36. 2010
    ..The observations support the model that persistence of PARP-1 at base excision repair intermediates, as cells move into S-phase, leads to DSBs and the attendant checkpoint responses...
  56. ncbi Mismatch repair proteins as sensors of alkylation DNA damage
    Jean Y J Wang
    Division of Hematology Oncology, Department of Medicine and Moores Cancer Center, University of California, San Diego, School of Medicine, 3855 Health Sciences Drive, La Jolla, California 92093, USA
    Cancer Cell 9:417-8. 2006
    ..and coworkers show that MMR complexes (MutSalpha and MutLalpha) are required for the recruitment of ATR-ATRIP to sites of alkylation damage, demonstrating that MMR complexes can function as sensors in DNA damage signal transduction.
  57. ncbi Selective loss of poly(ADP-ribose) and the 85-kDa fragment of poly(ADP-ribose) polymerase in nucleoli during alkylation-induced apoptosis of HeLa cells
    R Alvarez-Gonzalez
    Division of Tumor Virology, German Cancer Research Center, Heidelberg, Germany
    J Biol Chem 274:32122-6. 1999
    b>Alkylation treatment of HeLa cells results in the rapid induction of apoptosis as revealed by DNA laddering and cleavage of poly(ADP-ribose) polymerase (PARP) into the 29-and 85-kDa fragments (Kumari S. R., Mendoza-Alvarez, H...
  58. ncbi Biology of N-methylpyrrole-N-methylimidazole hairpin polyamide
    Musti Sree Rama Chandra Murty
    Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2 3 10 Surugadai, Kanda, Chiyoda ku, Tokyo 101 0062, Japan
    Biol Pharm Bull 27:468-74. 2004
    ..This review comprehensively discusses the current literature on using the sequence-specific recognition ability of the polyamides to study various DNA-protein interactions...
  59. pmc Site-directed alkylation of cysteine to test solvent accessibility of membrane proteins
    Lan Guan
    Department of Physiology, University of California Los Angeles, Los Angeles, California, USA
    Nat Protoc 2:2012-7. 2007
    ..radioactive thiol reagent N-[ethyl-1-14C]ethylmaleimide ([14C]NEM) is used to detect site-directed alkylation of engineered single-Cys mutants in situ...
  60. pmc A conserved domain of Schizosaccharomyces pombe dfp1(+) is uniquely required for chromosome stability following alkylation damage during S phase
    Amy D Fung
    Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada M5S 1A8
    Mol Cell Biol 22:4477-90. 2002
    ..damage response in addition to its well-characterized role in the initiation of DNA replication and that motif C plays a critical role in the response to alkylation damage, perhaps by restarting or stabilizing stalled replication forks.
  61. pmc Fission yeast Hsk1 (Cdc7) kinase is required after replication initiation for induced mutagenesis and proper response to DNA alkylation damage
    William P Dolan
    Molecular and Computational Biology Program, University of Southern California, Los Angeles, CA 90089, USA
    Genetics 185:39-53. 2010
    ..Both hsk1 and dfp1 mutants are acutely sensitive to alkylation damage yet defective in induced mutagenesis...
  62. ncbi The Bacillus subtilis counterpart of the mammalian 3-methyladenine DNA glycosylase has hypoxanthine and 1,N6-ethenoadenine as preferred substrates
    Randi M Aamodt
    Department of Molecular Biology, Institute of Medical Microbiology, University of Oslo, National Hospital, N 0027 Oslo, Norway
    J Biol Chem 279:13601-6. 2004
    ..It thus appears that bAag has a minor role in the repair of DNA alkylation damage and an important role in preventing the mutagenic effects of deaminated purines and cyclic etheno adducts ..
  63. ncbi A new deuterated alkylating agent for quantitative proteomics
    Roberto Sebastiano
    Department of Chemistry, Material and Engineering Chemistry, Politecnico of Milano, Via Mancinelli 7, Milano 20131, Italy
    Rapid Commun Mass Spectrom 17:2380-6. 2003
    ..alkylating agents such as iodoacetamide and non-charged acrylamide derivatives, such molecules achieve 100% alkylation of all -SH residues, even in complex proteins, without reacting with other functional groups...
  64. doi meta-Selective C-H bond alkylation with secondary alkyl halides
    Nora Hofmann
    Institut fur Organische und Biomolekulare Chemie, Georg August Universitat, Tammannstrasse 2, 37077 Gottingen, Germany
    J Am Chem Soc 135:5877-84. 2013
    ....
  65. ncbi Bacterial DNA repair genes and their eukaryotic homologues: 3. AlkB dioxygenase and Ada methyltransferase in the direct repair of alkylated DNA
    Jadwiga Nieminuszczy
    Department of Molecular Biology, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warszawa, Poland
    Acta Biochim Pol 54:459-68. 2007
    ..The product of ada gene, Ada protein, is an activator of transcription of all four genes. DNA bases damaged by alkylation are removed by distinct strategies...
  66. doi Scalable syntheses of both enantiomers of DNJNAc and DGJNAc from glucuronolactone: the effect of N-alkylation on hexosaminidase inhibition
    Andreas F G Glawar
    Oxford Glycobiology Institute, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK
    Chemistry 18:9341-59. 2012
    ....
  67. ncbi Time-dependent inactivation of P450 3A4 by raloxifene: identification of Cys239 as the site of apoprotein alkylation
    Brian R Baer
    Amgen, Department of Pharmacokinetics and Drug Metabolism, 1201 Amgen Court West, Seattle, Washington 98119, USA
    Chem Res Toxicol 20:954-64. 2007
    ..The change in protein mass of 471 Da combined with the protection from inactivation that occurred through pre-alkylation of Cys239 provided conclusive evidence that raloxifene-mediated P450 3A4 inactivation occurred through the ..
  68. doi Catalytic asymmetric alkylations of ketoimines. Enantioselective synthesis of N-substituted quaternary carbon stereogenic centers by Zr-catalyzed additions of dialkylzinc reagents to aryl-, alkyl-, and trifluoroalkyl-substituted ketoimines
    Peng Fu
    Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, USA
    J Am Chem Soc 130:5530-41. 2008
    ..readily and in >80% yield on gram scale through a two-step sequence from the corresponding ketones, undergo alkylation to afford quaternary alpha-amino esters in 79-97% ee...
  69. pmc Aag DNA glycosylase promotes alkylation-induced tissue damage mediated by Parp1
    Jennifer A Calvo
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
    PLoS Genet 9:e1003413. 2013
    ..Although base excision repair (BER) is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental...
  70. ncbi Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage
    Sarah C Trewick
    Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
    Nature 419:174-8. 2002
    ..Here we report that the highly conserved AlkB protein repairs DNA alkylation damage by means of an unprecedented mechanism...
  71. pmc Human ALKBH7 is required for alkylation and oxidation-induced programmed necrosis
    Dragony Fu
    Department of Biological Engineering, Department of Biology, Center for Environmental Health Sciences, David H Koch Center for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Genes Dev 27:1089-100. 2013
    ..Our results uncover a novel role for a mammalian AlkB homolog in programmed necrosis, presenting a new target for therapeutic intervention in cancer cells that are resistant to apoptotic cell death...
  72. doi Cobalt-catalyzed ortho alkylation of aromatic imines with primary and secondary alkyl halides
    Ke Gao
    Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore
    J Am Chem Soc 135:9279-82. 2013
    We report here cobalt-N-heterocyclic carbene catalytic systems for the ortho alkylation of aromatic imines with alkyl chlorides and bromides, which allows the introduction of a variety of primary and secondary alkyl groups at room ..
  73. doi Regioselective tandem N-alkylation/C-acylation of β,γ-alkynyl α-imino esters
    Isao Mizota
    Department of Chemistry for Materials, Graduate School of Engineering, Mie University, Tsu, Mie 514 8507, Japan
    Org Lett 15:4206-9. 2013
    ..The reaction exhibits broad substrate generality and unique regioselectivity. Moreover, synthesis of α-quaternary alkynyl amino esters was also carried out via oxidation of the intermediary enolate followed by alkylation.
  74. pmc Scope and limitations of auxiliary-assisted, palladium-catalyzed arylation and alkylation of sp2 and sp3 C-H bonds
    Enrico T Nadres
    Department of Chemistry, University of Houston, Houston, Texas 77204, United States
    J Org Chem 78:9689-714. 2013
    The scope of palladium-catalyzed, auxiliary-assisted direct arylation and alkylation of sp(2) and sp(3) C-H bonds of amine and carboxylic acid derivatives has been investigated...
  75. pmc Enantio-, diastereo-, and regioselective iridium-catalyzed asymmetric allylic alkylation of acyclic β-ketoesters
    Wen Bo Liu
    Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States
    J Am Chem Soc 135:17298-301. 2013
    The first regio-, diastereo-, and enantioselective allylic alkylation of acyclic β-ketoesters to form vicinal tertiary and all-carbon quaternary stereocenters is reported...
  76. pmc Iron-catalyzed heterocycle and arene deprotonative alkylation
    Ly Dieu Tran
    Department of Chemistry, University of Houston, Houston, Texas 77204 5003, USA
    Org Lett 12:4277-9. 2010
    A method for iron-catalyzed deprotonative alkylation of arene C-H bonds by alkyl iodides and bromides has been developed...
  77. doi Catalytic intermolecular allylic C-H alkylation
    Andrew J Young
    Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, Illinois 61801, USA
    J Am Chem Soc 130:14090-1. 2008
    The first electrophilic Pd(II)-catalyzed allylic C H alkylation is reported, providing a novel method for formation of sp3-sp3 C C bonds directly from C H bonds...
  78. doi Switchable reactivity of acylated alpha, beta-dehydroamino ester in the Friedel-Crafts alkylation of indoles by changing the Lewis acid
    Elena Angelini
    Institute of Medicinal Chemistry, University of Urbino Carlo Bo, Piazza del Rinascimento 6, 61029 Urbino PU, Italy
    J Org Chem 73:5654-7. 2008
    ..The orthogonal regioselectivity provides an efficient protocol toward highly functionalized 3-indolyl-alpha-amino acids. The mechanism of the reactions was explored by NMR studies...
  79. doi Chemo- and regioselectivity-tunable Pd-catalyzed allylic alkylation of imines
    Jian Ping Chen
    Shanghai Hong Kong Joint Laboratory in Chemical Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
    J Am Chem Soc 133:14180-3. 2011
    ..of cyclic and acyclic imines have been successfully applied as nucleophiles in the Pd-catalyzed allylic alkylation reaction...
  80. doi Asymmetric synthesis of an antagonist of neurokinin receptors: SSR 241586
    Thomas Xavier Métro
    Laboratoire de Chimie Organique, ESPCI ParisTech, CNRS, 10 rue Vauquelin, 75231 Paris Cedex 05, France
    J Org Chem 76:2594-602. 2011
    ..Different strategies have been studied to synthesize this molecule and among the strategies an organo-catalyzed Henry reaction, applied to an α-keto ester, has produced SSR 241586 in excellent enantiomeric excess...
  81. ncbi Effect of cations on the formation of DNA alkylation products in DNA reacted with 1-(2-Chloroethyl)-1-nitrosourea
    W J Bodell
    Brain Tumor Research Center of the Department of Neurological Surgery, University of California, San Francisco, California 94143 0555, USA
    Chem Res Toxicol 12:965-70. 1999
    The purpose of this study was to examine the influence of cations on the formation of the individual DNA alkylation products derived from 1-(2-chloroethyl)-1-nitrosourea (CNU)...
  82. pmc Alkylation of cysteine 468 in Stat3 defines a novel site for therapeutic development
    Ralf Buettner
    Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, California 91010, USA
    ACS Chem Biol 6:432-43. 2011
    ..Collectively, these findings suggest Cys468 in Stat3 represents a novel site for therapeutic intervention and demonstrates the promise of alkylation as a potentially effective chemical approach for Stat3-dependent cancers.
  83. doi Organic ligand-free alkylation of amines, carboxamides, sulfonamides, and ketones by using alcohols catalyzed by heterogeneous Ag/Mo oxides
    Xinjiang Cui
    Centre for Green Chemistry and Catalysis, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences Middle Tianshui Road, 18, Lanzhou, 730000, China
    Chemistry 17:1021-8. 2011
    ..The catalytic process shows promise for the efficient and economic synthesis of amine, carboxamide, sulfonamide, and ketone derivatives because of the simplicity of the system and ease of operation...
  84. doi Organometal additions to alpha-iminoesters: N-alkylation via umpolung
    Joshua S Dickstein
    Department of Chemistry, Roy and Diana Vagelos Laboratories, University of Pennsylvania, Philadelphia, PA 19104, USA
    Chem Soc Rev 37:1166-73. 2008
    ..While a significant body of work has focused on nucleophilic additions to the imine carbon (C-alkylation), a second pathway that involves nucleophilic reaction at the nitrogen (N-alkylation) is much less explored...
  85. ncbi Preventive effects of lupeol on DMBA induced DNA alkylation damage in mouse skin
    Nidhi Nigam
    Environmental Carcinogenesis Division, Industrial Toxicology Research Centre, P O Box 80, M G Marg, Lucknow 226001, India
    Food Chem Toxicol 45:2331-5. 2007
    ..26% prevention, at 96 h time interval, against DMBA induced DNA strand breakage. The results suggest preventive effects of lupeol on DMBA induced DNA alkylation damage in Swiss albino mice.
  86. doi The DinB•RecA complex of Escherichia coli mediates an efficient and high-fidelity response to ubiquitous alkylation lesions
    Tiziana M Cafarelli
    Department of Biology, Northeastern University, Boston, Massachusetts
    Environ Mol Mutagen 55:92-102. 2014
    b>Alkylation DNA lesions are ubiquitous, and result from normal cellular metabolism as well as from treatment with methylating agents and chemotherapeutics...
  87. pmc Merging photoredox catalysis with organocatalysis: the direct asymmetric alkylation of aldehydes
    David A Nicewicz
    Contribution from Merck Center for Catalysis, Department of Chemistry, Princeton University, Princeton, NJ 08544, USA
    Science 322:77-80. 2008
    ..Specifically, the enantioselective intermolecular alpha-alkylation of aldehydes has been accomplished using an interwoven activation pathway that combines both the photoredox ..
  88. pmc Genomic phenotyping of the essential and non-essential yeast genome detects novel pathways for alkylation resistance
    J Peter Svensson
    Biological Engineering Department, Center for Environmental Health Sciences, Biology Department, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    BMC Syst Biol 5:157. 2011
    ..Analysis of global transcriptional and phenotypic responses in the yeast S. cerevisiae provides means to identify pathways of damage recovery upon toxic exposure...
  89. ncbi A readily available chiral Ag-based N-heterocyclic carbene complex for use in efficient and highly enantioselective Ru-catalyzed olefin metathesis and Cu-catalyzed allylic alkylation reactions
    Joshua J Van Veldhuizen
    Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA 02467, USA
    J Am Chem Soc 127:6877-82. 2005
    ..In many cases, transformations promoted by the chiral NHC-based complexes proceed with higher enantioselectivity and reactivity than was observed with previously reported complexes...
  90. ncbi Solution structure and base perturbation studies reveal a novel mode of alkylated base recognition by 3-methyladenine DNA glycosylase I
    Chunyang Cao
    Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 2185, USA
    J Biol Chem 278:48012-20. 2003
    ..These findings indicate that base specific recognition by TAG does not involve strong pi-cation interactions, and suggest a novel mechanism for alkylated base recognition and removal...
  91. doi Synthesis of the tetracyclic core of tetrapetalone A enabled by a pyrrole reductive alkylation
    Andrew P Marcus
    Department of Chemistry, University of California, Berkeley, California 94720, USA
    Org Lett 12:4560-3. 2010
    The tetracyclic framework of the tetrapetalone A aglycon has been secured through synthesis. A reductive pyrrole alkylation enables the formation of a key tetrasubstituted carbon stereocenter, and the tetramic acid portion of the molecule ..
  92. pmc DNA crosslinking and biological activity of a hairpin polyamide-chlorambucil conjugate
    Yong Dong Wang
    Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Nucleic Acids Res 31:1208-15. 2003
    ..Polyamide 1-Chl conjugate (1-Chl) alkylates and interstrand crosslinks DNA in cell-free systems. The alkylation occurs predominantly at 5'-AGCTGCA-3' sequence, which represents the polyamide binding site...
  93. ncbi Synthesis of 2-substituted pyridines via a regiospecific alkylation, alkynylation, and arylation of pyridine N-oxides
    Hans Andersson
    Department of Chemistry, Umea University, SE 901 87 Umea, Sweden
    Org Lett 9:1335-7. 2007
    ..Furthermore, by exchanging acetic anhydride for DMF in the second step, 2-substituted pyridine N-oxides were obtained, as intermediates suitable for addition of a second Grignard reagent for the synthesis of 2,6-disubstituted pyridines...
  94. pmc A new protein superfamily includes two novel 3-methyladenine DNA glycosylases from Bacillus cereus, AlkC and AlkD
    Ingrun Alseth
    Department of Molecular Biology, Institute of Medical Microbiology and Centre of Molecular Biology and Neuroscience, University of Oslo, Rikshospitalet Radiumhospitalet HF, N 0027 Oslo, Norway
    Mol Microbiol 59:1602-9. 2006
    ..to environmental methylating agents such as methylchloride and may have special requirements for repair of alkylation damage on DNA...
  95. doi Amino acid-based synthesis of trifluoromethylalkene dipeptide isosteres by alcohol-assisted nucleophilic trifluoromethylation and organozinc-copper-mediated S(N)2' alkylation
    Kazuya Kobayashi
    Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo ku, Kyoto 606 8501, Japan
    J Org Chem 74:4626-9. 2009
    ..several CF(3)-ADIs were obtained through nucleophilic trifluoromethylation of gamma-keto esters and S(N)2' alkylation of trifluoromethylated mesylates...
  96. pmc Stereoselective alkylation of alpha,beta-unsaturated imines via C-H bond activation
    Denise A Colby
    Department of Chemistry, University of California, and Division of Chemical Sciences, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    J Am Chem Soc 128:5604-5. 2006
    The stereoselective alkylation of alpha,beta-unsaturated imines via C-H activation followed by imine hydrolysis produces tri- and tetrasubstituted alpha,beta-unsaturated aldehydes...
  97. pmc Selective N-alkylation of β-alanine facilitates the synthesis of a poly(amino acid)-based theranostic nanoagent
    Santimukul Santra
    NanoScience Technology Center, College of Medicine, Chemistry Department, University of Central Florida, Orlando, Florida 32826, United States
    Biomacromolecules 12:3917-27. 2011
    ....
  98. ncbi Deletion of the MAG1 DNA glycosylase gene suppresses alkylation-induced killing and mutagenesis in yeast cells lacking AP endonucleases
    W Xiao
    Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E5
    Mutat Res 487:137-47. 2001
    ..This rescuing effect appears to be specific for DNA alkylation damage, since the mag1 mutation reduces killing effects of two other DNA alkylating agents, but does not alter ..
  99. pmc Minor groove DNA alkylation directed by major groove triplex forming oligodeoxyribonucleotides
    E A Lukhtanov
    Epoch Pharmaceuticals Inc, 1725 220th Street SE, 104, Bothell, WA 98021, USA
    Nucleic Acids Res 25:5077-84. 1997
    We describe sequence-specific alkylation in the minor groove of double-stranded DNA by a hybridization-triggered reactive group conjugated to a triplex forming oligodeoxyribonucleotide (TFO) that binds in the major groove...
  100. doi Regioselective, borinic acid-catalyzed monoacylation, sulfonylation and alkylation of diols and carbohydrates: expansion of substrate scope and mechanistic studies
    Doris Lee
    Department of Chemistry, University of Toronto, 80 St George Street, Toronto ON M5S 3H6, Canada
    J Am Chem Soc 134:8260-7. 2012
    ..In addition, the scope of the selective acylation, sulfonylation, and alkylation is extended to 1,2- and 1,3-diols not derived from carbohydrates (28 examples); the efficiency, generality, and ..
  101. pmc Programmable sequence-specific click-labeling of RNA using archaeal box C/D RNP methyltransferases
    Migle Tomkuviene
    Department of Biological DNA Modification, Institute of Biotechnology, Vilnius University, Vilnius LT 02241, Lithuania
    Nucleic Acids Res 40:6765-73. 2012
    ..The described approach for the first time permits synthetically tunable sequence-specific labeling of RNA with single-nucleotide precision...

Research Grants66

  1. Anti-Inflammatory Glycosaminoglycan Ethers for Treatment of Periodontitis
    JUSTIN RODNEY SAVAGE; Fiscal Year: 2013
    ..a proprietary family of 5 kDa semi-synthetic glycosaminoglycan ethers (SAGEs), derived from sulfation and alkylation of hyaluronic acid (HA), that are intrinsically non-anticoagulant...
  2. Dopamine Transporter Structure and Function
    Christopher K Surratt; Fiscal Year: 2010
    ..accessibility of introduced cysteine residues of the mutant transporter proteins via immunoblotting and cysteine alkylation experiments, and immunochemical analysis of DAT proteolysates following covalent attachment of a series of novel ..
  3. Regulations of DNA Alkylation/Deamination Damage Repair
    Rabindra Roy; Fiscal Year: 2013
    ..interactions or post-translational modification may modulate the MPG-mediated repair of spontaneous and induced alkylation, deamination and peroxidation-induced DNA damage to combat genomic instability and cancer...
  4. Cigarette Smoke-derived Electrophilic Aldehydes and Airway Inflammation
    Albert van Der Vliet; Fiscal Year: 2013
    ..Acute mechanisms associated with direct and transient alkylation of redox-sensitive protein targets appear to be critical in this respect, diretly affecting activation of NF-?B ..
  5. The Roles of Trm9 and tRNA Methylation in the DNA Damage Response
    Thomas J Begley; Fiscal Year: 2010
    Some environmental toxicants are alkylating agents that can damage DNA. If left un-repaired, DNA alkylation damage can lead to mutation, cell death, and can promote carcinogenesis...
  6. TERPENE CONDENSATION REACTIONS
    CHARLES POULTER; Fiscal Year: 2009
    ..that catalyze these reactions belong to a large structurally diverse family of enzymes that mediate alkylation of nucleophilic carbon-carbon double bonds, aromatic rings, amino groups, hydroxyl groups, and thiol groups...
  7. Intra- and Extra-Chromosomal Probes for Mutagenesis by Carcinogens
    John M Essigmann; Fiscal Year: 2013
    ..cytosines (produced by oxidative stress), a series of N and 0-alkylated purines and pyrimidines (produced by alkylation and inflammation), and N2 and C8-purine aromatic amine adducts (produed by tobacco smoke)...
  8. Repair of oxidative DNA damage in mammalian cells
    Tadahide Izumi; Fiscal Year: 2013
    ..cell death, mutagenesis, and carcinogenesis caused by spontaneously formed DNA damage, such as oxidation and alkylation. Apurinic/apyrimidinic endonuclease (APE1 in mammals) arguably determines the BER rate in cells and thus plays a ..
  9. Oxidative activation of Src in smoke-induced epithelial mesenchymal transition
    Henry Jay Forman; Fiscal Year: 2013
    ..Our preliminary results support a mechanism for Src activation by CSE through oxidation or alkylation without Try529 dephosphorylation...
  10. Mechanisms of Sulfur Mustard Toxicology
    YIHUA JAN; Fiscal Year: 2010
    ..Sulfur mustard is a potent vesicant known to damage lung tissue. Toxicity is the result of alkylation of critical proteins that maintain the integrity of the lung, resulting in inflammation and oxidative stress...
  11. Role of poly (ADP-ribose)in the Repair of Ultraviolet Induced DNA Damage
    BRENEE SHEMEIR KING; Fiscal Year: 2012
    ..repair (BER), which repairs small, non-helix distorting lesions formed as a result of oxidation, deamination or alkylation, has been well established. Several papers have noted its direct interaction with proteins within the pathway (i...
  12. The Regulatory Role of PTEN on CXCR4-mediated Metastasis in Prostate Cancer Cells
    MAHANDRANAUTH ANAND CHETRAM; Fiscal Year: 2011
    ..this objective we will: (i) investigate whether ROS inactivates PTEN catalytic activity by performing a cysteine alkylation analysis and phosphatase activity assay;(ii) elucidate the mechanism by which ROS regulates CXCR4 and SDF1[..
  13. Mechanisms of selective excision and oxidative repair of alkylated DNA
    Manel Camps; Fiscal Year: 2013
    ..aim is to i) identify residues important for substrate discrimination using directed evolution under selective alkylation pressure, ii) determine crystal structures of ABH2 and MAG proteins in complex with 3mA- and eA-DNA, and iii) ..
  14. Novel approaches to enhance tumor cell cytotoxicity of alkylating agents
    Robert W Sobol; Fiscal Year: 2013
    ..Relevance: The proposed studies will provide new biomarkers of response to alkylation-induced DNA damage and cell death and provide insight into mechanisms that can be exploited to enhance response...
  15. A novel approach for quantitation of N-terminal valine adducts
    Gunnar Boysen; Fiscal Year: 2012
    ..proposed methodology can easily be extended to include additional adducts of interest and adapted to investigate alkylation at sites other than the N-terminal valine, providing a general analysis approach to understanding how reactive ..
  16. TERPENE CONDENSATION REACTIONS
    CHARLES DALE POULTER; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Prenyltransferases catalyze alkylation of carbon-carbon double bonds, aromatic rings, amino groups, hydroxyl groups, and thiol groups by allylic isoprenoid diphosphate esters...
  17. Carcinogenic Metabolites Formed from Antiestrogen
    Judy L Bolton; Fiscal Year: 2013
    ..of SERM quinoids will have a strong influence on which proteins are modified as well as sites of protein alkylation within the target proteins. 3...
  18. P450-Mediated Dehydrogenation Mechanisms
    Garold S Yost; Fiscal Year: 2013
    ..of the dehydrogenated intermediates are so reactive that they inactivate the P450 enzymes, generally through alkylation of active site nucleophilic residues...
  19. Regulation of the DNA damage Response
    Karlene A Cimprich; Fiscal Year: 2013
    ..These proteins exert their effects in a damage-specific manner, responding to alkylation damage and UV damage with complementary specificities, yet the mechanisms by which they act remain undefined...
  20. Role of Promotor Polymorphisms of the MGMT Gene in Alkylation Chemotherapy
    Sherif Z Abdel Rahman; Fiscal Year: 2010
    ..Alteration in MGMT transcription would significantly influence sensitivity to alkylation chemotherapy and the outcome of GB treatment...
  21. EUKARYOTIC DNA ALKYLATION REPAIR
    Leona D Samson; Fiscal Year: 2013
    ..of a competitive renewal application for the continuation of a more than twenty year old project to study DNA alkylation repair in eukaryotic cells...
  22. Molecular basis for ligation of mismatched DNA ends
    Gilbert Chu; Fiscal Year: 2012
    ..randomly misincorporates cysteines into the targeted protein, and then identifies exposed cysteine residues by alkylation. This will permit high-throughput mapping of exposed residues that are buried by protein-protein interactions...
  23. The Role of Ape1 in Neurotoxicity of Cancer Treatments
    Mark R Kelley; Fiscal Year: 2012
    ..and function after injury by chemotherapy or IR and helps to maintain normal neuronal function by minimizing alkylation and oxidative damage to DNA as well as by regulating the activity of AP1, NFkB and p53...
  24. The influence of DNA repair on inflammation associated carcinogenesis
    Leona D Samson; Fiscal Year: 2013
    ..RONS are known to induce damaged DNA bases, either directly via oxidation, deamination and indirectly via alkylation damage...
  25. Ruthenium-based antimalarial agents
    ROBERTO A SANCHEZ-DELGADO; Fiscal Year: 2013
    ..Ru-trioxane and Ru-(bis) trioxane complexes as potential non-toxic antimalarial agents acting by radical alkylation mechanisms. 3...
  26. Structural Biochemistry of DNA Dealkylation
    John A Tainer; Fiscal Year: 2012
    ..DNA alkylation repair is critical for genome stability and furthermore a major resistance factor for cancer chemotherapies, so ..
  27. Improving etoposide treatment of Ewing's sarcoma
    ALEXANDER JAMES BISHOP; Fiscal Year: 2013
    ..Indeed, we already successfully used this strategy to identify novel alkylation survival genes and pathways in mouse and human cells and demonstrated that pathways critical in Drosophila are ..
  28. Inflammation and the Ubiquitin/Proteasome Pathway in Neurodegeneration.
    MARIA EMILIA FIGUEIREDO PEREIRA; Fiscal Year: 2010
    ..Electrophile binding (S-alkylation) by endogenous compounds such as PGJ2 is regarded as playing an important role in determining whether neurons ..
  29. The role of MRP1 in Protection of Cardiac Injury
    Mary Vore; Fiscal Year: 2012
    ..Finally, Aim 4 will characterize the ability of HNEand GS-HNE to inactivate Mrp1 by alkylation of key cysteine, histidine or lysine residues...
  30. Comparing and contrasting the biology of damage survival at a genomic level
    ALEXANDER JAMES BISHOP; Fiscal Year: 2010
    ..Indeed, we already successfully used this strategy to identify novel alkylation survival genes and pathways in mouse and human cells and demonstrated that pathways critical in Drosophila are ..
  31. BIOACTIVATION OF HALOGENATED HYDROCARBONS
    F Peter Guengerich; Fiscal Year: 2013
    ..of butadiene diepoxide and the hypothesis that this is a prominent electrophilic species involved in DNA alkylation and genotoxicity of butadiene diepoxide (as opposed to a detoxication product)...
  32. Chemical Approaches to Protein Phosphorylation
    Philip A Cole; Fiscal Year: 2013
    ..We will employ a newly developed method to install methylthiocarbamyl (MTC) acetyl-Lys mimics by Cys alkylation and analyze the biochemical effects...
  33. Tetrahydroisoquinoline Antitumor Drugs: Synthesis and Biosynthesis
    Robert Michael Williams; Fiscal Year: 2012
    ..This is particularly evident in the case of Et-743. Plans are presented to mechanistically separate the DNA alkylation and cross-linking chemistry of these agents from their capacity to inflict oxidative damage on cells...
  34. Bioinspired Enantioselective Catalytic alpha-Alkylation of Aldehydes
    SEAN M KEDROWSKI; Fiscal Year: 2013
    ..Direct, enantioselective, catalytic ?-alkylation of carbon is one of the most fundamental ways to form new carbon-carbon bonds...
  35. Hypoxia-Activated O6-Benzylguanine Prodrugs
    ALAN CLAYTON SARTORELLI; Fiscal Year: 2012
    ..The DNA lesion, produced by the cholorethylating agents, an alkylation of the O6-position of DNA guanine which leads to a G-C crosslink, is susceptible to repair by O6-alkylguanine-..
  36. Total Synthesis of Bioactive Marine Natural Products
    Armen Zakarian; Fiscal Year: 2013
    ..Within the first two areas, we will extend the utility of chiral lithium reagents for asymmetric alkylation reactions wih dianionic intermediates...
  37. New Radiation-Activated Antitumor Agents That Target Hypoxia
    Xiaohua Peng; Fiscal Year: 2010
    ..Their DNA-damage profiles and mechanism with respect to cross-link formation and DNA alkylation will be studied...
  38. Novel Targets in Cancer Chemotherapy: Chemical Biology of Guanine Alkylation
    Michael P Stone; Fiscal Year: 2013
    ....
  39. Non-coding RNA Structure through a Mutate-and-Map Strategy
    Rhiju Das; Fiscal Year: 2013
    ..M2 to two additional chemistries, flavin-mononucleotide-induced photo-oxidation (M2-FMN) and dimethyl-sulfate alkylation (M2-DMS)...
  40. NF-kB1-p50 in the response to DNA alkylation damage
    Bakhtiar Yamini; Fiscal Year: 2013
    ..abstract_text> ..
  41. Biotransformation of Estrogens to Carcinogenic Quinoids
    JUDY BOLTON; Fiscal Year: 2005
    ..What is the predominant mechanism of catechol estrogen-induced DNA damage? Oxidation versus alkylation. Using synthetic oligonucleotides with defined sequences, we will explore the effect of time, concentration, ..
  42. Nanopore Detection of DNA Damage
    Henry S White; Fiscal Year: 2013
    ..processes that introduce epigenetic markers as well as exposure to DNA damaging agents through oxidation and alkylation reactions from endogenous sources or toxicants...
  43. SIGNIFICANCE OF EPOXIDE GENERATED 3-ALKYL-URACIL IN DNA
    JEROME SOLOMON; Fiscal Year: 1999
    We have discovered a new class of DNA adducts, 3-alkyl uracil residues, which are the product of cytosine alkylation and deamination by a variety of aliphatic epoxides...
  44. DNA REPAIR AND SUSCEPTIBILITY TO ENVIRONMENTAL AGENTS
    Ivan Rusyn; Fiscal Year: 2004
    ..Exposure to environmental agents may result in oxidative and alkylation damage leading to formation of a number of mutagenic DNA adducts...
  45. Metal-Catalyzed Cross Coupling with N,O-Acetals and Acetals
    ABIGAIL GUTMANN DOYLE; Fiscal Year: 2013
    ..we will pursue catalyst design and development for enantioselective arylation, heteroarylation, and alkylation of readily available and stable N,O-acetals and acetals using organoboronate and organozinc reagents (Specific ..
  46. ION DEREGULATION IN VIVO AND INJURY BY ALKYLATING DRUGS
    George Corcoran; Fiscal Year: 1990
    ..frequently result from highly reactive metabolites that initiate a lethal biological cascade by widespread alkylation. With descriptive aspects of this discovery well investigated, attention now focuses on prevention of this form ..
  47. ARCHITECTURE OF ERYTHROCYTE SKELETON--BILAYER INTERFACE
    STEPHEN SHOHET; Fiscal Year: 2000
    ..Novel methodologic approaches include: alkylation of thiophosphorylated phosphorylation sites to label ankyrin and band 3; a fluoresceinated recombinant 52-amino ..
  48. Synthesis of Macrolides, Steroids, Cyclopentanoids, etc.
    BARRY TROST; Fiscal Year: 2009
    ..These new synthetic methods apply to many structural types beyond those illustrated and constitutes a significant to gain access to complex molecular targets more easily. ..
  49. COLLAGENS OF HYALINE CARTILAGE
    Richard Mayne; Fiscal Year: 1992
    ..the past year, three genetically distinct chains were fractionated from both HMW and LMW after reduction and alkylation of interchain disulfide bridges...
  50. New Methods for Direct Carbon-Hydrogen Bond Functionalization
    OLAFS DAUGULIS; Fiscal Year: 2013
    ..In this project, palladium-catalyzed arylation, alkylation, vinylation, and alkynylation of unactivated sp3 C-H bonds will be explored in context of synthesis of ..
  51. Molecular Libraries from Imidazole-4,5-Dicarboxylic Acid
    PAUL BAURES; Fiscal Year: 2009
    ..and diester combinations, 2) to deliver analogs of the first specific aim modified by imidazole ring alkylation, functional group derivitization around a bioactive lead, and by removing protecting groups to yield 322 ..
  52. Synthesis of the Apoptosis-Inducing Alkaloid Monanchocidin
    RYAN LLOYD PATMAN; Fiscal Year: 2013
    ..strategy is proposed to address the synthesis of this molecule employing palladium catalyzed asymmetric allylic alkylation (AAA) and a novel hydroguanidination/cyclization sequence...
  53. Imaging of O6-Alkylguanine-DNA Alkyltransferase
    Ganesan Vaidyanathan; Fiscal Year: 2005
    ..The drug resistance is due to the repair of DNA lesions, generated by alkylation of guanine and thymine residues by the alkylating agents, by the repair protein O6 alkyl-DNA alkyltrasferase (..
  54. Preparative Radical Chemistry for Biomedical Research
    Phil S Baran; Fiscal Year: 2013
    ..the second part outlines the development of zinc bis(alkanesulfinate) reagents for (hetero)arene alkylation, as well as the bis- functionalization of hetero(arene)s using a sequential addition strategy;and 3) the final ..
  55. Enhanced Fluoropolymer Membrane Reactors for Production of Pharmaceutical Interme
    Ning Shangguan; Fiscal Year: 2011
    ..The resultant MR will be used to run reactions of pharmaceutical interest such as the alkylation and nitration of aromatic compounds...
  56. Enhanced Fluoropolymer Membrane Reactors for Production of Pharmaceutical Interme
    Ning Shangguan; Fiscal Year: 2012
    ..The resultant MR will be used to run reactions of pharmaceutical interest such as the alkylation and nitration of aromatic compounds...
  57. PROPERTIES OF CHEMICALLY MODIFIED PHOSPHOLIPASE A-2
    Philip Rosenberg; Fiscal Year: 1993
    ..Modifications to be performed include: 1. alkylation and methylation of histidine at the enzymatic active site, 2...
  58. Ethyl Pyruvate: A Novel Treatment for Sepsis
    RUSSELL DELUDE; Fiscal Year: 2006
    ..These hypotheses are: the ROS Hypothesis, the Alkylation Hypothesis, and the Glutathione (GSH) Depletion Hypothesis...
  59. BIOPHYSICAL AND SCANNING FORCE MICROSCOPY STUDIES
    DOROTHY ERIE; Fiscal Year: 2001
    ..Such lesions result from a variety of endogenous and exogenous agents that cause the oxidation, alkylation, or hydrolysis of bases...
  60. DEVELOPING ISONITRILE CHEMISTRY FOR MEDICINAL APPLICATIONS
    FRASER FERGUSSON FLEMING; Fiscal Year: 2012
    ..Preliminary results demonstrate the viability of two different, but complementary, alkylation strategies to access bioactive isonitriles...
  61. APPLICATION OF CRYSTALLOGRAPHIC TECHNIQUES
    JENNY GLUSKER; Fiscal Year: 2002
    DESCRIPTION: Three aspects of chemical carcinogenesis will be investigated: the structural effect on DNA of alkylation by a bulky activated carcinogenic polycyclic aromatic hydrocarbon (PAH) and the reason that it escapes enzymatic repair,..
  62. DNA DAMAGE DURING AGING OF POSTMITOTIC CELLS
    JAMES GAUBATZ; Fiscal Year: 1990
    The primary objective of the proposed research is to investigate alkylation damage and repair in several postmitotic tissues of the C57BL/6Nia inbred mouse strain as a function of age...
  63. The Synthesis of Bioactive Polycyclic Natural Products
    Brian M Stoltz; Fiscal Year: 2013
    ..this grant application is focused on a) the development of new palladium- and copper-catalyzed enantio-selective alkylation and protonation reactions that produce important building blocks for synthesis, b) the utilization of these ..
  64. Selective C-H Bond Functionalization in Complex Organic Synthesis
    Dalibor Sames; Fiscal Year: 2010
    ..Also, two new approaches to cross-coupling of sp3 C-H bonds and alkenes (1-alkylation of saturated heterocycles) will be pursued: first, the intermolecular transition metal-catalyzed alkylation;and ..
  65. A Flexible and Concise Approach to the Citrinadins: Total Synthesis of Citrinadin
    DEVON ALLEN MUNDAL; Fiscal Year: 2012
    ..annulation process involving a Lewis acid-mediated aza-Payne rearrangement and aziridinium-opening pyridone alkylation to rapidly assemble the densely functionalized C, D and E rings of the citrinadins...
  66. CARBOCATIONS AND BIO-RELATED REACTIONS
    GEORGE OLAH; Fiscal Year: 1993
    ..the most significant type of reactive organic intermediates and investigate representative in vitro cyclization, alkylation, and rearrangement reactions of biologically significant systems in which these ions play a significant role...