Laurence P G Wakelin

Summary

Affiliation: University of New South Wales
Country: Australia

Publications

  1. pmc Crystal structure of 9-amino-N-[2-(4-morpholinyl)ethyl]-4-acridinecarboxamide bound to d(CGTACG)2: implications for structure-activity relationships of acridinecarboxamide topoisomerase poisons
    Adrienne Adams
    Department of Biochemistry, University of Sydney, Sydney, NSW 2006, Australia
    Nucleic Acids Res 30:719-25. 2002
  2. pmc Intracellular trafficking as a determinant of AS-DACA cytotoxicity in rhabdomyosarcoma cells
    Steven J Wolf
    Biospecimens Research and Tumour Bank, Children s Cancer Research Unit, The Children s Hospital at Westmead, Westmead, NSW 2774, Australia
    BMC Cell Biol 12:36. 2011
  3. ncbi request reprint Kinetic studies of the binding of acridinecarboxamide topoisomerase poisons to DNA: implications for mode of binding of ligands with uncharged chromophores
    Laurence P G Wakelin
    School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia
    J Med Chem 45:894-901. 2002
  4. ncbi request reprint Bisintercalating threading diacridines: relationships between DNA binding, cytotoxicity, and cell cycle arrest
    Laurence P G Wakelin
    School of Medical Sciences, and the School of Women s and Children s Health, University of New South Wales, Sydney 2052, New South Wales, Australia
    J Med Chem 46:5790-802. 2003
  5. doi request reprint DNA threading bis(9-aminoacridine-4-carboxamides): effects of piperidine sidechains on DNA binding, cytotoxicity and cell cycle arrest
    Zhicong He
    School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia
    Bioorg Med Chem 16:4390-400. 2008
  6. doi request reprint Human α1-adrenoceptor subtype selectivity of substituted homobivalent 4-aminoquinolines
    Junli Chen
    Department of Pharmacology, School of Medical Sciences, Wallace Wurth Building, UNSW Australia, Sydney, NSW 2052, Australia Electronic address
    Bioorg Med Chem 22:5910-6. 2014
  7. doi request reprint α₁-Adrenoceptor and serotonin 5-HT(1A) receptor affinity of homobivalent 4-aminoquinoline compounds: an investigation of the effect of linker length
    Junli Chen
    Department of Pharmacology, School of Medical Sciences, UNSW, Sydney, NSW 2052, Australia
    Biochem Pharmacol 85:1534-41. 2013
  8. doi request reprint [Co(III)(cyclen)Cl2]Cl is selectively cytotoxic to human leukaemia cells
    Zhicong He
    School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
    Eur J Pharmacol 637:11-5. 2010
  9. pmc Novel DNA topoisomerase IIα inhibitors from combined ligand- and structure-based virtual screening
    Malgorzata N Drwal
    Department of Pharmacology, School of Medical Sciences, UNSW Australia, Sydney, NSW, Australia
    PLoS ONE 9:e114904. 2014
  10. doi request reprint The solution structure of bis(phenazine-1-carboxamide)-DNA complexes: MLN 944 binding corrected and extended
    Andre Serobian
    Department of Pharmacology, School of Medical Sciences, Faculty of Medicine, UNSW Australia, Sydney, 2052, NSW, Australia
    Biopolymers 101:1099-113. 2014

Collaborators

  • Junli Chen
  • W A Denny
  • P Kovacic
  • B C Baguley
  • Adrienne Adams
  • Giovanni Capranico
  • Malgorzata N Drwal
  • Zhicong He
  • Amin M S Abdul Majid
  • Andre Serobian
  • Renate Griffith
  • Steven J Wolf
  • Bernard W Stewart
  • George Smythe
  • Susana C M Teixeira
  • Donald S Thomas
  • Graham E Ball
  • Stefano G Manzo
  • Jessica Marinello
  • Tony Huynh
  • Yves Pommier
  • Nicole S Bryce
  • Keli Agama
  • Trevor W Hambley
  • Daniel R Catchpoole
  • Donna Lai
  • Alexandra Eleftheriou
  • Malik Zihlif
  • Zhang Qing
  • Xianyong Bu
  • Christine J Cardin
  • James H Thorpe
  • Harold R Powell
  • Alan K Todd

Detail Information

Publications16

  1. pmc Crystal structure of 9-amino-N-[2-(4-morpholinyl)ethyl]-4-acridinecarboxamide bound to d(CGTACG)2: implications for structure-activity relationships of acridinecarboxamide topoisomerase poisons
    Adrienne Adams
    Department of Biochemistry, University of Sydney, Sydney, NSW 2006, Australia
    Nucleic Acids Res 30:719-25. 2002
    ..We discuss our findings with respect to the potential role played by the interaction of the drug side chain and the topoisomerase II protein in the poisoning of topoisomerase activity by the acridinecarboxamides...
  2. pmc Intracellular trafficking as a determinant of AS-DACA cytotoxicity in rhabdomyosarcoma cells
    Steven J Wolf
    Biospecimens Research and Tumour Bank, Children s Cancer Research Unit, The Children s Hospital at Westmead, Westmead, NSW 2774, Australia
    BMC Cell Biol 12:36. 2011
    ..Here, we investigate the basis for this selectivity, and demonstrate in these RMS lines, and in an AS-DACA- resistant subclone of RH30, that AS-DACA-induced cytotoxicity correlates with the induction of DNA double strand breaks...
  3. ncbi request reprint Kinetic studies of the binding of acridinecarboxamide topoisomerase poisons to DNA: implications for mode of binding of ligands with uncharged chromophores
    Laurence P G Wakelin
    School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia
    J Med Chem 45:894-901. 2002
    ..This difference may have relevance to the ability of DACA to be a dual poison of both topoisomerases I and II...
  4. ncbi request reprint Bisintercalating threading diacridines: relationships between DNA binding, cytotoxicity, and cell cycle arrest
    Laurence P G Wakelin
    School of Medical Sciences, and the School of Women s and Children s Health, University of New South Wales, Sydney 2052, New South Wales, Australia
    J Med Chem 46:5790-802. 2003
    ..There are no simple relationships between structure, cytotoxicity, and cell cycle arrest, and the origins of this complexity are unclear given that the compounds bind to DNA by a common mechanism...
  5. doi request reprint DNA threading bis(9-aminoacridine-4-carboxamides): effects of piperidine sidechains on DNA binding, cytotoxicity and cell cycle arrest
    Zhicong He
    School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia
    Bioorg Med Chem 16:4390-400. 2008
    ..Measurements with supercoiled DNA indicate that they bisintercalate...
  6. doi request reprint Human α1-adrenoceptor subtype selectivity of substituted homobivalent 4-aminoquinolines
    Junli Chen
    Department of Pharmacology, School of Medical Sciences, Wallace Wurth Building, UNSW Australia, Sydney, NSW 2052, Australia Electronic address
    Bioorg Med Chem 22:5910-6. 2014
    ....
  7. doi request reprint α₁-Adrenoceptor and serotonin 5-HT(1A) receptor affinity of homobivalent 4-aminoquinoline compounds: an investigation of the effect of linker length
    Junli Chen
    Department of Pharmacology, School of Medical Sciences, UNSW, Sydney, NSW 2052, Australia
    Biochem Pharmacol 85:1534-41. 2013
    ..The limited α(1D)-AR and 5-HT(1A)-R affinity of these compounds makes them promising leads for future drug development of α(1A)-AR selective ligands without α(1D)-AR and the 5-HT(1A)-R off-target activity...
  8. doi request reprint [Co(III)(cyclen)Cl2]Cl is selectively cytotoxic to human leukaemia cells
    Zhicong He
    School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
    Eur J Pharmacol 637:11-5. 2010
    ....
  9. pmc Novel DNA topoisomerase IIα inhibitors from combined ligand- and structure-based virtual screening
    Malgorzata N Drwal
    Department of Pharmacology, School of Medical Sciences, UNSW Australia, Sydney, NSW, Australia
    PLoS ONE 9:e114904. 2014
    ..Thus, our study confirms the applicability of computer-aided methods for the discovery of novel topoisomerase II poisons, and presents compounds which could be investigated further as selective topoisomerase IIα inhibitors. ..
  10. doi request reprint The solution structure of bis(phenazine-1-carboxamide)-DNA complexes: MLN 944 binding corrected and extended
    Andre Serobian
    Department of Pharmacology, School of Medical Sciences, Faculty of Medicine, UNSW Australia, Sydney, 2052, NSW, Australia
    Biopolymers 101:1099-113. 2014
    ..The dynamics simulations reveal extensive solvent interactions involving the linker amines, the carboxamide group, and the DNA bases. © 2014 Wiley Periodicals, Inc. Biopolymers 101: 1099-1113, 2014. ..
  11. pmc Exploring DNA topoisomerase I ligand space in search of novel anticancer agents
    Malgorzata N Drwal
    Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, Australia
    PLoS ONE 6:e25150. 2011
    ..Although the tested compounds display only low in vitro antitumour activity, our approach has been successful in the identification of structurally novel Top1 inhibitors worthy of further investigation as potential anticancer agents...
  12. doi request reprint Mass spectrometry studies of the binding of the minor groove-directed alkylating agent alkamin to AT-tract oligonucleotides
    Amin M S Abdul Majid
    School of Molecular Sciences, Department of Pharmacology, and Bioanalytical Mass Spectrometry Facility, University of New South Wales, NSW 2052, Australia
    Chem Res Toxicol 22:146-57. 2009
    ....
  13. ncbi request reprint Structure of 9-amino-[N-(2-dimethylamino)propyl]acridine-4-carboxamide bound to d(CGTACG)(2): a comparison of structures of d(CGTACG)(2) complexed with intercalatorsin the presence of cobalt
    Adrienne Adams
    School of Molecular and Microbial Biosciences, University of Sydney, NSW 2006, Australia
    Acta Crystallogr D Biol Crystallogr 60:823-8. 2004
    ..Given the nature of the ligands found in these complexes, the relevance of the quadruplex structure to the biological activity of those agents, known to be topoisomerase poisons, is questioned...
  14. ncbi request reprint Mechanisms of action of DNA intercalating acridine-based drugs: how important are contributions from electron transfer and oxidative stress?
    Bruce C Baguley
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1000, New Zealand
    Curr Med Chem 10:2643-9. 2003
    ..Such reactions may make important contributions to the antitumor activity of these drugs...
  15. ncbi request reprint Structural characterisation of bisintercalation in higher-order DNA at a junction-like quadruplex
    Susana C M Teixeira
    School of Chemistry, The University of Reading, Whiteknights, Berkshire, RG6 6AD, Reading, UK
    J Mol Biol 323:167-71. 2002
    ..This higher-order DNA structure provides insight into an unexpected property of bisintercalating threading agents, and suggests the idea of targeting such compounds specifically at four-way DNA junctions...
  16. ncbi request reprint Structure of the d(CGCGAATTCGCG)2 complex of the minor groove binding alkylating agent alkamin studied by mass spectrometry
    Amin M S Abdul Majid
    School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang, Malaysia corrected
    Mol Pharmacol 71:1165-78. 2007
    ..We conclude that the marked cytotoxicity of alkamin and its experimental antitumor activity could be the consequence of its ability to cross-link cellular DNA at AT tract sequences...