Stephen Neidle

Summary

Affiliation: University of London
Country: UK

Publications

  1. doi request reprint Human telomeric G-quadruplex: the current status of telomeric G-quadruplexes as therapeutic targets in human cancer
    Stephen Neidle
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, London, UK
    FEBS J 277:1118-25. 2010
  2. doi request reprint The structures of quadruplex nucleic acids and their drug complexes
    Stephen Neidle
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    Curr Opin Struct Biol 19:239-50. 2009
  3. doi request reprint Quadruplex DNA crystal structures and drug design
    Stephen Neidle
    The Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London, WC1N 1AX, UK
    Biochimie 90:1184-96. 2008
  4. doi request reprint Rational design of acridine-based ligands with selectivity for human telomeric quadruplexes
    Silvia Sparapani
    CR UK Biomolecular Structure Group, The School of Pharmacy, University of London, London WC1N 1AX, UK
    J Am Chem Soc 132:12263-72. 2010
  5. doi request reprint Rational design of substituted diarylureas: a scaffold for binding to G-quadruplex motifs
    William C Drewe
    The Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    J Med Chem 51:7751-67. 2008
  6. pmc Targeting human gastrointestinal stromal tumor cells with a quadruplex-binding small molecule
    Mekala Gunaratnam
    CRUK Biomolecular Structure Group, School of Pharmacy, University of London, London, WC1N 1AX, U K
    J Med Chem 52:3774-83. 2009
  7. doi request reprint Targeting telomerase and telomeres: a click chemistry approach towards highly selective G-quadruplex ligands
    Adam D Moorhouse
    CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London, UK
    Mol Biosyst 4:629-42. 2008
  8. ncbi request reprint Trisubstituted acridines as G-quadruplex telomere targeting agents. Effects of extensions of the 3,6- and 9-side chains on quadruplex binding, telomerase activity, and cell proliferation
    Michael J B Moore
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, London WC1N 1AX, UK
    J Med Chem 49:582-99. 2006
  9. doi request reprint The prenylated dioxopiperazine alkaloid Cristatin A has selective telomeric DNA G-quadruplex stabilising properties
    Khondaker M Rahman
    Department of Pharmacy, King s College London, Stamford Street, London, SE18WA, UK
    Chem Commun (Camb) 48:8760-2. 2012
  10. ncbi request reprint Evaluation of by disubstituted acridone derivatives as telomerase inhibitors: the importance of G-quadruplex binding
    R John Harrison
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    Bioorg Med Chem Lett 14:5845-9. 2004

Collaborators

Detail Information

Publications99

  1. doi request reprint Human telomeric G-quadruplex: the current status of telomeric G-quadruplexes as therapeutic targets in human cancer
    Stephen Neidle
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, London, UK
    FEBS J 277:1118-25. 2010
    ..This minireview summarizes the available data on these compounds and the challenges posed for drug discovery...
  2. doi request reprint The structures of quadruplex nucleic acids and their drug complexes
    Stephen Neidle
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    Curr Opin Struct Biol 19:239-50. 2009
    ..Structures for a few of these are now available, which emphasise the role played by loop sequences in determining fold...
  3. doi request reprint Quadruplex DNA crystal structures and drug design
    Stephen Neidle
    The Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London, WC1N 1AX, UK
    Biochimie 90:1184-96. 2008
    ..Implications for drug design are discussed, in the context of the druggability of both telomeric and non-telomeric quadruplex DNAs...
  4. doi request reprint Rational design of acridine-based ligands with selectivity for human telomeric quadruplexes
    Silvia Sparapani
    CR UK Biomolecular Structure Group, The School of Pharmacy, University of London, London WC1N 1AX, UK
    J Am Chem Soc 132:12263-72. 2010
    ....
  5. doi request reprint Rational design of substituted diarylureas: a scaffold for binding to G-quadruplex motifs
    William C Drewe
    The Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    J Med Chem 51:7751-67. 2008
    ....
  6. pmc Targeting human gastrointestinal stromal tumor cells with a quadruplex-binding small molecule
    Mekala Gunaratnam
    CRUK Biomolecular Structure Group, School of Pharmacy, University of London, London, WC1N 1AX, U K
    J Med Chem 52:3774-83. 2009
    ..Molecular modeling studies with a telomeric quadruplex have been used to rationalize aspects of the experimental quadruplex melting data...
  7. doi request reprint Targeting telomerase and telomeres: a click chemistry approach towards highly selective G-quadruplex ligands
    Adam D Moorhouse
    CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London, UK
    Mol Biosyst 4:629-42. 2008
    ..duplex DNA. The ability of these ligands to inhibit the enzymatic activity of telomerase correlates with their ability to stabilize quadruplex DNA, and with estimates of affinity calculated by molecular modeling...
  8. ncbi request reprint Trisubstituted acridines as G-quadruplex telomere targeting agents. Effects of extensions of the 3,6- and 9-side chains on quadruplex binding, telomerase activity, and cell proliferation
    Michael J B Moore
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, London WC1N 1AX, UK
    J Med Chem 49:582-99. 2006
    ....
  9. doi request reprint The prenylated dioxopiperazine alkaloid Cristatin A has selective telomeric DNA G-quadruplex stabilising properties
    Khondaker M Rahman
    Department of Pharmacy, King s College London, Stamford Street, London, SE18WA, UK
    Chem Commun (Camb) 48:8760-2. 2012
    ..Crucially, the molecule is more drug-like than most previously identified quadruplex-binding agents, and provides a unique chemical scaffold for future chemical biology and drug discovery studies...
  10. ncbi request reprint Evaluation of by disubstituted acridone derivatives as telomerase inhibitors: the importance of G-quadruplex binding
    R John Harrison
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    Bioorg Med Chem Lett 14:5845-9. 2004
    ..It is concluded that telomerase inhibitory activity is a necessary though by itself insufficient property in order for cellular growth arrest to occur at sub-toxic concentrations, and that tight quadruplex binding is also required...
  11. doi request reprint Structure-based design and evaluation of naphthalene diimide G-quadruplex ligands as telomere targeting agents in pancreatic cancer cells
    Marialuisa Micco
    The School of Pharmacy, University College London, London WC1N 1AX, UK
    J Med Chem 56:2959-74. 2013
    ....
  12. doi request reprint Structural basis for telomeric G-quadruplex targeting by naphthalene diimide ligands
    Gavin W Collie
    CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, London, WC1N 1AX, United Kingdom
    J Am Chem Soc 134:2723-31. 2012
    ....
  13. ncbi request reprint A G-quadruplex telomere targeting agent produces p16-associated senescence and chromosomal fusions in human prostate cancer cells
    Christopher M Incles
    Cancer Research UK Biomolecular Structure Group, School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    Mol Cancer Ther 3:1201-6. 2004
    ..We also show that treatment with BRACO-19 causes extensive end-to-end chromosomal fusions, consistent with telomere uncapping...
  14. ncbi request reprint Structure-based design of benzylamino-acridine compounds as G-quadruplex DNA telomere targeting agents
    Cristina Martins
    CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, United Kingdom
    Bioorg Med Chem Lett 17:2293-8. 2007
    ..Replacement of the previously reported anilino substituents by benzylamino groups results in enhanced quadruplex interaction, and for one compound, superior telomerase inhibitory activity...
  15. doi request reprint Topology conservation and loop flexibility in quadruplex-drug recognition: crystal structures of inter- and intramolecular telomeric DNA quadruplex-drug complexes
    Gary N Parkinson
    The Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    J Mol Biol 381:1145-56. 2008
    ..Ligands are bound into the external TTA loop nucleotides and stack onto G-tetrad surfaces. These crystal structures provide a framework for further ligand development of the naphthalene diimide series to enhance selectivity and affinity...
  16. doi request reprint Targeting pancreatic cancer with a G-quadruplex ligand
    Mekala Gunaratnam
    CRUK Biomolecular Structure Unit, The School of Pharmacy, University of London, London WC1N 1AX, UK
    Bioorg Med Chem 19:7151-7. 2011
    ..It is proposed that the simultaneous targeting of these quadruplexes may be an effective anti-tumor strategy...
  17. doi request reprint Molecular basis of structure-activity relationships between salphen metal complexes and human telomeric DNA quadruplexes
    Nancy H Campbell
    CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 29 Brunswick Square, London WC1N 1AX, U K
    J Med Chem 55:209-22. 2012
    ..The complexes show significant antiproliferative activity for the compounds in a panel of cancer cell lines. They also show telomerase inhibitory activity in the telomerase TRAP-LIG assay...
  18. doi request reprint An evaluation cascade for G-quadruplex telomere targeting agents in human cancer cells
    Mekala Gunaratnam
    The Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, London, UK
    Methods Mol Biol 613:303-13. 2010
    ..These assays evaluate quadruplex stabilisation properties, short- and long-term cell viability, telomerase enzymatic activity, cellular senescence, and telomere length changes...
  19. doi request reprint Tri- and tetra-substituted naphthalene diimides as potent G-quadruplex ligands
    Francisco Cuenca
    CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    Bioorg Med Chem Lett 18:1668-73. 2008
    ..They inhibit telomerase in the TRAP assay, and show potent senescence-based short-term anti-proliferative effects on MCF7 and A549 cancer cell lines, and localize in the nucleus and particularly the nucleolus of MCF7 cells...
  20. ncbi request reprint Mechanism of acridine-based telomerase inhibition and telomere shortening
    Mekala Gunaratnam
    CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    Biochem Pharmacol 74:679-89. 2007
    ..It is concluded that the cellular activity of BRACO-19 can be ascribed both to the uncapping of 3' telomere ends and to telomere shortening that may preferentially affect cells with short telomeres...
  21. doi request reprint Design, synthesis and evaluation of 4,5-di-substituted acridone ligands with high G-quadruplex affinity and selectivity, together with low toxicity to normal cells
    Francisco Cuenca
    CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London, UK
    Bioorg Med Chem Lett 19:5109-13. 2009
    ..They have low toxicity against a panel of cancer cell lines and a normal human fibroblast line, and produce potent senescence-based long-term growth arrest in the MCF7 and A549 cancer cell lines...
  22. doi request reprint Structure-activity relationships of monomeric C2-aryl pyrrolo[2,1-c][1,4]benzodiazepine (PBD) antitumor agents
    Dyeison Antonow
    Cancer Research UK Gene Targeted Drug Design Research Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, U K
    J Med Chem 53:2927-41. 2010
    ..This analogue (14l) was shown to delay tumor growth in a HCT-116 (bowel) human tumor xenograft model...
  23. pmc Sequence occurrence and structural uniqueness of a G-quadruplex in the human c-kit promoter
    Alan K Todd
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    Nucleic Acids Res 35:5799-808. 2007
    ..The c-kit87 quadruplex thus fulfils a fundamental criterion of a 'good' drug target, in that it possesses distinctive three-dimensional structural features that are only present in at most a handful of other genes...
  24. ncbi request reprint Acquired cellular resistance to flavopiridol in a human colon carcinoma cell line involves up-regulation of the telomerase catalytic subunit and telomere elongation. Sensitivity of resistant cells to combination treatment with a telomerase inhibitor
    Christopher M Incles
    The School of Pharmacy, 29 39 Brunswick Square, London WC1N 1AX, UK
    Mol Pharmacol 64:1101-8. 2003
    ....
  25. doi request reprint A novel series of G-quadruplex ligands with selectivity for HIF-expressing osteosarcoma and renal cancer cell lines
    Caterina M Lombardo
    UCL School of Pharmacy, University College London, 29 39 Brunswick Square, London WC1N 1AX, UK
    Bioorg Med Chem Lett 22:5984-8. 2012
    ....
  26. doi request reprint Structural basis of DNA quadruplex recognition by an acridine drug
    Nancy H Campbell
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, United Kingdom
    J Am Chem Soc 130:6722-4. 2008
    ..The structure rationalizes the existing structure-activity data and provides a starting-point for the structure-based design of quadruplex-binding ligands..
  27. doi request reprint Structure-based design of selective high-affinity telomeric quadruplex-binding ligands
    Caterina Maria Lombardo
    CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, London WC1N 1AX, UK
    Chem Commun (Camb) 46:9116-8. 2010
    ..Binding affinities, estimated by electrospray mass spectrometry, are in accord with the design concept...
  28. doi request reprint Electrospray mass spectrometry of telomeric RNA (TERRA) reveals the formation of stable multimeric G-quadruplex structures
    Gavin W Collie
    CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, WC1N 1AX London, United Kingdom
    J Am Chem Soc 132:9328-34. 2010
    ..The importance of kinetic effects in multimer formation, unfolding, and structural rearrangements is also highlighted...
  29. pmc Small-molecule binding to the DNA minor groove is mediated by a conserved water cluster
    Dengguo Wei
    UCL School of Pharmacy, 29 39 Brunswick Square, London WC1N 1AX, United Kingdom
    J Am Chem Soc 135:1369-77. 2013
    ..Features of the water cluster and observed differences in binding modes help to explain the measured binding affinities and thermodynamic characteristics of these ligands on binding to AT sites in DNA...
  30. ncbi request reprint Synthesis of distamycin A polyamides targeting G-quadruplex DNA
    Michael J B Moore
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London, UK WC1N 1AX
    Org Biomol Chem 4:3479-88. 2006
    ..Quadruplex affinity increases with the number of pyrrole groups, and it is suggested that this is consistent with a mixed groove/G-quartet stacking binding mode...
  31. pmc Quadruplex DNA: sequence, topology and structure
    Sarah Burge
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    Nucleic Acids Res 34:5402-15. 2006
    ..Such information, together with biological insights, will be important for the discovery of drugs targeting quadruplexes from particular genes...
  32. ncbi request reprint G-quadruplex compounds and cis-platin act synergistically to inhibit cancer cell growth in vitro and in vivo
    Mekala Gunaratnam
    CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London, WC1N 1AX, UK
    Biochem Pharmacol 78:115-22. 2009
    ....
  33. ncbi request reprint Virtual screening of DNA minor groove binders
    David A Evans
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    J Med Chem 49:4232-8. 2006
    ....
  34. pmc A crystallographic and modelling study of a human telomeric RNA (TERRA) quadruplex
    Gavin W Collie
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    Nucleic Acids Res 38:5569-80. 2010
    ..The computations, based on the native crystal structure, provide an explanation for RNA G-quadruplex ligand binding selectivity for a group of naphthalene diimide ligands as compared to the DNA G-quadruplex...
  35. doi request reprint TRAP-LIG, a modified telomere repeat amplification protocol assay to quantitate telomerase inhibition by small molecules
    Julie Reed
    CRUK Biomolecular Structure Group, School of Pharmacy, University of London, London WC1N 1AX, UK
    Anal Biochem 380:99-105. 2008
    ....
  36. ncbi request reprint Chemical approaches to the discovery and development of cancer therapies
    Stephen Neidle
    Cancer Research UK, Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    Nat Rev Cancer 5:285-96. 2005
    ....
  37. pmc Molecular dynamics and principal components analysis of human telomeric quadruplex multimers
    Shozeb Haider
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, London, United Kingdom
    Biophys J 95:296-311. 2008
    ..The addition of a ligand to the model confirms the hypothesis that flat planar chromophores stabilize G-quadruplex structures by making them less flexible...
  38. doi request reprint Tetrasubstituted naphthalene diimide ligands with selectivity for telomeric G-quadruplexes and cancer cells
    Sonja M Hampel
    CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, London WC1N 1AX, UK
    Bioorg Med Chem Lett 20:6459-63. 2010
    ..The compounds have potent activity in a panel of cancer cell lines, with typical IC(50) values of ∼0.1 μM, and up to 100-fold lower toxicity in a normal human fibroblast cell line...
  39. pmc Putative DNA quadruplex formation within the human c-kit oncogene
    Sarah Rankin
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    J Am Chem Soc 127:10584-9. 2005
    ..The c-kit quadruplex may be a new target for therapeutic intervention in cancers where there is elevated expression of the c-kit gene...
  40. ncbi request reprint Targeting the DNA minor groove with fused ring dicationic compounds: comparison of in silico screening and a high-resolution crystal structure
    Nancy H Campbell
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, London WC1N 1AX, UK
    Bioorg Med Chem Lett 16:15-9. 2006
    ..36 Angstrom. Conditions for reliable in silico docking that reproduce the observed position of the ligand in the minor groove have been determined...
  41. doi request reprint Structural basis of telomeric RNA quadruplex--acridine ligand recognition
    Gavin W Collie
    CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, London, United Kingdom
    J Am Chem Soc 133:2721-8. 2011
    ..W.; Haider, S. M.; Neidle, S.; Parkinson, G. N. Nucleic Acids Res. 2010, 38, 5569 - 5580), which have implications for the future design of small molecules targeting TERRA quadruplexes, and RNA quadruplexes more generally...
  42. doi request reprint Crystallography of DNA and RNA G-quadruplex nucleic acids and their ligand complexes
    Nancy Campbell
    Cancer Research UK Biomolecular Structure Group, The UCL School of Pharmacy, London, United Kingdom
    Curr Protoc Nucleic Acid Chem . 2012
    ..This article focuses on the crystallization of quadruplexes and their complexes with small-molecule ligands. Protocols for successful crystallization, as used in the author's laboratory, are described in detail...
  43. doi request reprint Selectivity in ligand recognition of G-quadruplex loops
    Nancy H Campbell
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    Biochemistry 48:1675-80. 2009
    ..We conclude that the nature of the loop has a significant influence on ligand selectivity for particular quadruplex folds...
  44. ncbi request reprint Observation of the coexistence of sodium and calcium ions in a DNA G-quadruplex ion channel
    Michael P H Lee
    CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, U K
    J Am Chem Soc 129:10106-7. 2007
  45. doi request reprint A molecular model for drug binding to tandem repeats of telomeric G-quadruplexes
    Shozeb M Haider
    CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, London, UK
    Biochem Soc Trans 37:583-8. 2009
    ..The present paper reports on a molecular modelling study that uses Molecular Dynamics simulation methods to build dimer and tetramer quadruplex repeats. These incorporate ligand-binding sites and are models for overhang-ligand complexes...
  46. pmc Predictive modelling of topology and loop variations in dimeric DNA quadruplex structures
    Pascale Hazel
    CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    Nucleic Acids Res 34:2117-27. 2006
    ..The simulations suggest an explanation for the distinct patterns of observed dimer topology for sequences with T3 and T2 loops, which depend on the loop lengths, rather than only on G-quartet stability...
  47. doi request reprint Molecular modeling and simulation of G-quadruplexes and quadruplex-ligand complexes
    Shozeb Haider
    The Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, London, UK
    Methods Mol Biol 608:17-37. 2010
    ..The scope and limitations of these approaches are discussed...
  48. ncbi request reprint Synthesis, biophysical and biological evaluation of 3,6-bis-amidoacridines with extended 9-anilino substituents as potent G-quadruplex-binding telomerase inhibitors
    Christoph M Schultes
    Cancer Research UK Biomolecular Structure Group, University of London School of Pharmacy, 29 39 Brunswick Square, London WC1N 1AX, UK
    Bioorg Med Chem Lett 14:4347-51. 2004
    ..Furthermore, a direct correlation between the FRET and TRAP assays was observed, supporting the use of the rapid screening FRET assay for early assessment of potential G4-stabilising telomerase inhibitors...
  49. ncbi request reprint Structure of a G-quadruplex-ligand complex
    Shozeb M Haider
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, WC1N 1AX, London, UK
    J Mol Biol 326:117-25. 2003
    ..It is held in place by a combination of stacking interactions and specific hydrogen bonds with thymine bases. The stability of the ligand in this binding site has been confirmed by a 2ns molecular dynamics simulation...
  50. ncbi request reprint Stabilization of G-quadruplex DNA by highly selective ligands via click chemistry
    Adam D Moorhouse
    Department of Pharmaceutical and Biological Chemistry, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, United Kingdom
    J Am Chem Soc 128:15972-3. 2006
    ..Furthermore, a modified TRAP assay has shown that some of these compounds also inhibit telomerase at low micromolar concentration...
  51. pmc Crystal structure of a c-kit promoter quadruplex reveals the structural role of metal ions and water molecules in maintaining loop conformation
    Dengguo Wei
    CRUK Biomolecular Structure Group, UCL School of Pharmacy, University College London, 29 39 Brunswick Square, WC1N 1AX, London, UK
    Nucleic Acids Res 40:4691-700. 2012
    ..This difference can be understood by the stabilizing role of structured water networks...
  52. doi request reprint Molecular modeling on inhibitor complexes and active-site dynamics of cytochrome P450 C17, a target for prostate cancer therapy
    Shozeb M Haider
    CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    J Mol Biol 400:1078-98. 2010
    ..The work also describes the results of docking synthetic inhibitors, including the drug abiraterone and the natural substrate pregnenolone, in the CYP17 active site together with molecular dynamics simulations on the complexes...
  53. ncbi request reprint Structural basis for binding of porphyrin to human telomeres
    Gary N Parkinson
    CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, United Kingdom
    Biochemistry 46:2390-7. 2007
    ..Implications for the design of quadruplex-binding ligands are discussed, together with a model for the formation of anaphase bridges, which are observed following cellular treatment with TMPyP4...
  54. ncbi request reprint Studies on the nitroreductase prodrug-activating system. Crystal structures of complexes with the inhibitor dicoumarol and dinitrobenzamide prodrugs and of the enzyme active form
    Eric Johansson
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, United Kingdom
    J Med Chem 46:4009-20. 2003
    ..Finally, modulating substrate specificity by alteration of the structure of the enzyme rather than the prodrug might usefully focus on modifying the Phe124 residue and those surrounding it...
  55. ncbi request reprint Trisubstituted acridine derivatives as potent and selective telomerase inhibitors
    R John Harrison
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London, WC1N 1AX, U K
    J Med Chem 46:4463-76. 2003
    ..These data support a model for the action of these compounds that involves the stabilization of intermediate quadruplex structures that inhibit the elongation of telomeric DNA by telomerase in tumor cells...
  56. doi request reprint Fluorine in medicinal chemistry: β-fluorination of peripheral pyrrolidines attached to acridine ligands affects their interactions with G-quadruplex DNA
    Nancy H Campbell
    The School of Pharmacy, University of London, 29 39 Brunswick Square, London, UK WC1N 1AX
    Org Biomol Chem 9:1328-31. 2011
    ....
  57. ncbi request reprint Topology variation and loop structural homology in crystal and simulated structures of a bimolecular DNA quadruplex
    Pascale Hazel
    Cancer Research U K Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    J Am Chem Soc 128:5480-7. 2006
    ..These can be classified into two discrete conformational classes, suggesting that these represent preferred loop conformations that are independent of crystal-packing forces...
  58. ncbi request reprint Truncated azinomycin analogues intercalate into DNA
    Maxwell A Casely-Hayford
    Department of Pharmaceutical and Biological Chemistry, School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    Bioorg Med Chem Lett 15:653-6. 2005
    ..Both the designed azinomycin analogue 4 and the natural product 3 bind to DNA and cause unwinding, supporting an intercalative mode of binding...
  59. doi request reprint Bis-guanylhydrazone diimidazo[1,2-a:1,2-c]pyrimidine as a novel and specific G-quadruplex binding motif
    Silvia Sparapani
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, London, WC1N 1AX, UK
    Chem Commun (Camb) 46:5680-2. 2010
    ..Molecular modeling suggests that the guanylhydrazone groups play an active role in quadruplex binding...
  60. doi request reprint Identification of novel telomeric G-quadruplex-targeting chemical scaffolds through screening of three NCI libraries
    Khondaker M Rahman
    The School of Pharmacy, University of London, London, United Kingdom
    Bioorg Med Chem Lett 22:3006-10. 2012
    ..Thus they provide new chemical scaffolds for the development of novel classes of G-quadruplex-targeting agents...
  61. ncbi request reprint The structure of telomeric DNA
    Stephen Neidle
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, WC1N 1AX, London, UK
    Curr Opin Struct Biol 13:275-83. 2003
    ..This can, at least in vitro, fold into a wide variety of four-stranded quadruplex structures, many of whose arrangements are being revealed by crystallographic and NMR studies...
  62. pmc Highly prevalent putative quadruplex sequence motifs in human DNA
    Alan K Todd
    CRUK Biomolecular Structure Group, The School of Pharmacy, University of London 29 39 Brunswick Square, London WC1N 1AX, UK
    Nucleic Acids Res 33:2901-7. 2005
    ..Being able to highlight types of potential quadruplex sequences in G-rich regions is an important step in searching for biologically relevant sequences and finding their function...
  63. ncbi request reprint Telomerase inhibitors in cancer therapy: current status and future directions
    Christopher M Incles
    Cancer Research UK Biomolecular Structure Group, School of Pharmacy, University of London, 29 39 Brunswick Square, London, WC1N 1AX, UK
    Curr Opin Investig Drugs 4:675-85. 2003
    ..The principal approaches of catalytic inhibitors, antisense to the template, and folding of the DNA substrate, are reviewed and critically evaluated for their potential in anticancer therapy...
  64. ncbi request reprint Stephen Neidle on cancer therapy and G-quadruplex inhibitors. Interview by Joanna De Souza
    Stephen Neidle
    The School of Pharmacy, University of London, School of Pharmacy, 29 39 Brunswick Square, London WC1N 1AX, UK
    Drug Discov Today 9:778-81. 2004
    b>Stephen Neidle was educated at Imperial College, London, where he graduated in chemistry and then proceeded to do a PhD in crystallography...
  65. doi request reprint G-quadruplexes and metal ions
    Nancy H Campbell
    The School of Pharmacy, University of London, London, WC1N 1AX, UK
    Met Ions Life Sci 10:119-34. 2012
    ..Three categories of quadruplex are examined, tetramolecular, bimolecular, and intramolecular: all are formed by telomeric nucleic acid sequences from human or ciliate organisms...
  66. doi request reprint Surface area accessibility and the preferred topology of telomeric DNA quadruplex-ligand complexes
    Shozeb M Haider
    CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, London, UK
    Biochimie 93:1275-9. 2011
    ..It is suggested that this approach, which does not depend on energy functions, can be useful in the rational design of topology-specific ligands, especially in the case of polymorphic quadruplexes...
  67. ncbi request reprint Loop-length-dependent folding of G-quadruplexes
    Pascale Hazel
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    J Am Chem Soc 126:16405-15. 2004
    ..Multiple conformations of each structure are likely to coexist in solution, as they were calculated to have very similar free energies...
  68. pmc The relationship of potential G-quadruplex sequences in cis-upstream regions of the human genome to SP1-binding elements
    Alan K Todd
    CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    Nucleic Acids Res 36:2700-4. 2008
    ....
  69. pmc Bioactive pyridine-N-oxide disulfides from Allium stipitatum
    Gemma O'Donnell
    Centre for Pharmacognosy and Phytotherapy, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    J Nat Prod 72:360-5. 2009
    ..This compound was also assessed in a mouse model for in vivo toxicity...
  70. doi request reprint A novel small-molecule inhibitor of IL-6 signalling
    Giovanna Zinzalla
    Cancer Research UK Protein, The School of Pharmacy, University of London, London, United Kingdom
    Bioorg Med Chem Lett 20:7029-32. 2010
    ..It was also selectively cytostatic in MDA-MB-231 (STAT3-dependent) versus A4 (STAT3-null) cells suggesting STAT3-specific inhibitory properties...
  71. ncbi request reprint Fundamentals of DNA and RNA structure
    Stephen Neidle
    Structural Biology Section, CRC Biomolecular Structure Unit, Institute of Cancer Research, London, UK
    Methods Biochem Anal 44:41-73. 2003
  72. pmc Mapping the sequences of potential guanine quadruplex motifs
    Alan K Todd
    CRUK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    Nucleic Acids Res 39:4917-27. 2011
    ....
  73. ncbi request reprint Telomere maintenance as a target for anticancer drug discovery
    Stephen Neidle
    CRC Biomolecular Structure Unit, Chester Beatty Laboratories, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK
    Nat Rev Drug Discov 1:383-93. 2002
    ..Here, we describe the current understanding of telomere biology, and the application of this knowledge to the development of anticancer drugs...
  74. pmc Protein and drug interactions in the minor groove of DNA
    Zdenek Moravek
    Faculty of Mathematics and Physics, Charles University, Ke Karlovu 5, Prague, Czech Republic
    Nucleic Acids Res 30:1182-91. 2002
    ..DNA deformation concentrates on dinucleotide regions with a distinct deformation of the delta and epsilon backbone torsion angles for the Asn and delta, epsilon, zeta and chi for the Phe-contacted regions...
  75. ncbi request reprint Structure of an unprecedented G-quadruplex scaffold in the human c-kit promoter
    Anh Tuân Phan
    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Am Chem Soc 129:4386-92. 2007
    ..This unique structural scaffold provides a highly specific platform for the future design of ligands specifically targeted to the promoter DNA of c-kit...
  76. ncbi request reprint Strong binding in the DNA minor groove by an aromatic diamidine with a shape that does not match the curvature of the groove
    Binh Nguyen
    Department of Chemistry, Georgia State University, Atlanta, Georgia 30303, USA
    J Am Chem Soc 124:13680-1. 2002
    ..Complementary and consistent results were obtained from both the X-ray and molecular dynamics studies; both of these methods reveal direct and water-mediated H-bonds between the ligand and the DNA...
  77. ncbi request reprint Solid-phase synthesis of symmetrical 3,6-bispeptide-acridone conjugates
    Sylvain Ladame
    University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK
    Org Lett 4:2509-12. 2002
    ..This strategy will enable the generation of a library of 3,6-bispeptide-acridones to be screened for selective binding to telomeric G-quadruplex DNA...
  78. pmc Induced fit conformational changes of a "reversed amidine" heterocycle: optimized interactions in a DNA minor groove complex
    Manoj Munde
    Department of Chemistry, Georgia State University, P O Box 4098, Atlanta, Georgia 30302 4098, USA
    J Am Chem Soc 129:5688-98. 2007
    ..The structural results and molecular modeling studies provide an explanation for the differences in binding affinities for related amidine and reversed amidine analogues...
  79. ncbi request reprint Thiophene-based diamidine forms a "super" at binding minor groove agent
    Sirish Mallena
    Department of Chemistry, Georgia State University, P O Box 4098, Atlanta, Georgia 30302 4098, USA
    J Am Chem Soc 126:13659-69. 2004
    ....
  80. pmc A conserved quadruplex motif located in a transcription activation site of the human c-kit oncogene
    Himesh Fernando
    Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, United Kingdom
    Biochemistry 45:7854-60. 2006
    ..Collectively, the evidence suggests that this quadruplex is a serious target for a detailed functional investigation at the cell-biology level...
  81. ncbi request reprint Chemical variation of natural-product-like scaffolds: design, synthesis, and biological activity of fused bicyclic acetal derivatives
    Lech Gustav Milroy
    Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK
    Angew Chem Int Ed Engl 46:2493-6. 2007
  82. ncbi request reprint Crystal structure of the potassium form of an Oxytricha nova G-quadruplex
    Shozeb Haider
    The Cancer Research UK Biomolecular Structure Unit, Chester Beatty Laboratories, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK
    J Mol Biol 320:189-200. 2002
    ..Each quadruplex has five potassium ions organised in a linear channel, with square antiprismatic coordination to each ion from oxygen atoms...
  83. ncbi request reprint Crystal structure of parallel quadruplexes from human telomeric DNA
    Gary N Parkinson
    The Cancer Research UK Biomolecular Structure Unit, Chester Beatty Laboratories, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK
    Nature 417:876-80. 2002
    ..This DNA structure suggests a straightforward path for telomere folding and unfolding, as well as ways in which it can recognize telomere-associated proteins...
  84. ncbi request reprint A G-quadruplex-interactive potent small-molecule inhibitor of telomerase exhibiting in vitro and in vivo antitumor activity
    Sharon M Gowan
    Cancer Research Campaign CRC Center for Cancer Therapeutics, Institute of Cancer Research, Surrey, United Kingdom
    Mol Pharmacol 61:1154-62. 2002
    ....
  85. pmc High-resolution crystal structure of the intramolecular d(TpA) thymine-adenine photoadduct and its mechanistic implications
    R Jeremy H Davies
    School of Biological Sciences, School of Chemistry and Chemical Engineering, Queen s University, Belfast BT7 1NN, UK
    Nucleic Acids Res 35:1048-53. 2007
    ..It is probable that the primary photoreaction is mechanistically analogous to pyrimidine dimerization despite having a much lower quantum yield...
  86. ncbi request reprint Structure-specific recognition of quadruplex DNA by organic cations: influence of shape, substituents and charge
    Elizabeth W White
    Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA
    Biophys Chem 126:140-53. 2007
    ..ITC results indicate that binding is largely enthalpy driven. Circular dichroism was also used to identify a group of structurally related compounds that selectively target quadruplex grooves...
  87. ncbi request reprint Stabilization of G-quadruplex DNA and inhibition of telomerase activity by square-planar nickel(II) complexes
    Julie E Reed
    Department of Chemistry, Imperial College London, South Kensington, UK
    J Am Chem Soc 128:5992-3. 2006
    ..FRET studies have shown that these complexes have a remarkable ability to stabilize G-quadruplex DNA. Furthermore, TRAP/Taq assays have shown that these complexes inhibit telomerase at low micromolar concentrations...
  88. ncbi request reprint Amide bond direction modulates G-quadruplex recognition and telomerase inhibition by 2,6 and 2,7 bis-substituted anthracenedione derivatives
    Giuseppe Zagotto
    Department of Pharmaceutical Sciences, University of Padova, Via Marzolo, 5, 35131 Padova, Italy
    Bioorg Med Chem 16:354-61. 2008
    ..A more extended planar surface would allow more efficient stacking interactions with the quadruplex structure, hence more effective telomerase inhibition...
  89. ncbi request reprint Out-of-shape DNA minor groove binders: induced fit interactions of heterocyclic dications with the DNA minor groove
    Yi Miao
    Department of Chemistry, Georgia State University, Atlanta, Georgia 30303, USA
    Biochemistry 44:14701-8. 2005
    ..This result suggests that traditional views of compound curvature required for minor groove complex formation should be reevaluated...
  90. ncbi request reprint Natural and synthetic G-quadruplex interactive berberine derivatives
    Marco Franceschin
    Dipartimento di Chimica, Universita di Roma La Sapienza, Piazzale A Moro 5, 00185 Rome, Italy
    Bioorg Med Chem Lett 16:1707-11. 2006
    ..The results show that these molecules have selectivity for G-quadruplex compared to duplex DNA, and that their aromatic moieties play a dominant role in quadruplex binding...
  91. pmc Exploring the recognition of quadruplex DNA by an engineered Cys2-His2 zinc finger protein
    Sylvain Ladame
    University Chemical Laboratories, University of Cambridge, UK
    Biochemistry 45:1393-9. 2006
    ..Modeling also suggests that an important role of the key protein finger residues in the Gq1-quadruplex complex is to maintain Gq1 in an optimum conformation for quadruplex recognition...
  92. ncbi request reprint Synthesis and evaluation of analogues of 10H-indolo[3,2-b]quinoline as G-quadruplex stabilising ligands and potential inhibitors of the enzyme telomerase
    Berangere Guyen
    The School of Chemistry, Queen s University Belfast, Belfast, UK BT9 5AG
    Org Biomol Chem 2:981-8. 2004
    ..It is concluded that this class of compound represents a new chemical type suitable for further development as telomerase inhibitors...
  93. ncbi request reprint New mustard-linked 2-aryl-bis-benzimidazoles with anti-proliferative activity
    Christine Le Sann
    School of Chemistry, Queen s University Belfast, Stranmillis Road, Belfast, UK BT9 5AG
    Org Biomol Chem 4:1305-12. 2006
    ..The in vitro activities of these compounds against five cancer cell lines are also provided...
  94. ncbi request reprint Sequence-selective targeting of long stretches of the DNA minor groove by a novel dimeric bis-benzimidazole
    Alexandra Joubert
    INSERM U 524 et Laboratoire de Pharmacologie Antitumorale du Centre Oscar Lambret, IRCL, Place de Verdun, 59045 Lille, France
    Biochemistry 42:5984-92. 2003
    ..Compound 5 does not show acute cellular cytotoxicity, in contrast with its monomeric bis-benzimidazole precursors, yet is rapidly taken up into cells...
  95. ncbi request reprint DNA sequence specificity of triplex-binding ligands
    Melanie D Keppler
    Division of Biochemistry and Molecular Biology, School of Biological Sciences, University of Southampton, UK
    Eur J Biochem 270:4982-92. 2003
    ..Triplexes containing alternating C+GC and TAT triplets are not stabilized by ligands as they would interrupt the alternating pattern of charged and uncharged residues...
  96. doi request reprint Aminoacyl-anthraquinone conjugates as telomerase inhibitors: synthesis, biophysical and biological evaluation
    Giuseppe Zagotto
    Department of Pharmaceutical Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy
    J Med Chem 51:5566-74. 2008
    ..These results are of help in the rational design of more efficient G-quadruplex stabilizers, possibly endowed with cancer cell-selective antiproliferative effects...
  97. ncbi request reprint The G-quadruplex-interactive molecule BRACO-19 inhibits tumor growth, consistent with telomere targeting and interference with telomerase function
    Angelika M Burger
    Institute for Experimental Oncology, Freiburg, Germany
    Cancer Res 65:1489-96. 2005
    ..The in vitro and in vivo data presented here is consistent with the G-quadruplex binding ligand BRACO-19 producing an anticancer effect by inhibiting the capping and catalytic functions of telomerase...
  98. ncbi request reprint Tetrapeptides induce selective recognition for G-quadruplexes when conjugated to a DNA-binding platform
    Sylvain Ladame
    University Chemical Laboratory, University of Cambridge, UK
    Org Biomol Chem 2:2925-31. 2004
    ..These studies indicate that targeting distinct features of a G-quadruplex with hybrid molecules is a promising strategy for discriminating between quadruplex and duplex DNA...
  99. ncbi request reprint The design of G-quadruplex ligands as telomerase inhibitors
    Javier Cuesta
    Cancer Research UK Biomolecular Structure Unit, Chester Beatty Laboratories, The Institute of Cancer Research, London SW3 6JB, UK
    Mini Rev Med Chem 3:11-21. 2003
    ..Implications for anti-tumour therapy with such molecules are discussed, and the particular challenges and problems discussed...