A hitchhiker's guide to G-quadruplex ligands.

Over the past decade, nucleic acid chemists have seen the spectacular emergence of molecules designed to interact efficiently and selectively with a peculiar DNA structure named G-quadruplex. Initially derived from classical DNA intercalators, these G-quadruplex ligands progressively became the focal point of new excitement since they appear to inhibit selectively the growth of cancer cells thereby opening interesting perspectives towards the development of novel anti-cancer drugs. The present article aims to help researchers enter this exciting research field, and to highlight recent advances in the design of G-quadruplex ligands.

[1]  N. Maizels,et al.  Gene function correlates with potential for G4 DNA formation in the human genome , 2006, Nucleic acids research.

[2]  S. Balasubramanian,et al.  Oxazole-based peptide macrocycles: a new class of G-quadruplex binding ligands. , 2006, Journal of the American Chemical Society.

[3]  Gary Parkinson,et al.  Telomere maintenance as a target for anticancer drug discovery , 2002, Nature Reviews Drug Discovery.

[4]  James M. Morrell,et al.  Evaluation of by disubstituted acridone derivatives as telomerase inhibitors: the importance of G-quadruplex binding. , 2004, Bioorganic & medicinal chemistry letters.

[5]  Julie E Reed,et al.  Stabilization of G-quadruplex DNA and inhibition of telomerase activity by square-planar nickel(II) complexes. , 2006, Journal of the American Chemical Society.

[6]  S. Balasubramanian,et al.  Macrocyclic and helical oligoamides as a new class of G-quadruplex ligands. , 2007, Journal of the American Chemical Society.

[7]  Stephen Neidle,et al.  Structure of a G-quadruplex-ligand complex. , 2003, Journal of molecular biology.

[8]  K. Shin‐ya,et al.  Telomerase inhibition with a novel G-quadruplex-interactive agent, telomestatin: in vitro and in vivo studies in acute leukemia , 2006, Oncogene.

[9]  E. De Pauw,et al.  Ascididemin and meridine stabilise G-quadruplexes and inhibit telomerase in vitro. , 2005, Biochimica et biophysica acta.

[10]  O. Fedoroff,et al.  NMR-Based model of a telomerase-inhibiting compound bound to G-quadruplex DNA. , 1998, Biochemistry.

[11]  Jean-Louis Mergny,et al.  Selective recognition of G-qQuadruplex telomeric DNA by a bis(quinacridine) macrocycle. , 2003, Journal of the American Chemical Society.

[12]  Stephen Neidle,et al.  A G-quadruplex telomere targeting agent produces p16-associated senescence and chromosomal fusions in human prostate cancer cells. , 2004, Molecular cancer therapeutics.

[13]  J. Mergny,et al.  Quadruplex-based molecular beacons as tunable DNA probes. , 2006, Journal of the American Chemical Society.

[14]  K. Shin‐ya.  Novel Antitumor and Neuroprotective Substances Discovered by Characteristic Screenings Based on Specific Molecular Targets , 2005, Bioscience, biotechnology, and biochemistry.

[15]  W. Rutter,et al.  Unusual DNA structure of the diabetes susceptibility locus IDDM2 and its effect on transcription by the insulin promoter factor Pur-1/MAZ. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[16]  J. Chaires,et al.  Molecular recognition of nucleic acids: Coralyne binds strongly to poly(A) , 2005, FEBS letters.

[17]  J. Mergny,et al.  Highly efficient G-quadruplex recognition by bisquinolinium compounds. , 2007, Journal of the American Chemical Society.

[18]  S. Cogoi,et al.  G-quadruplex formation within the promoter of the KRAS proto-oncogene and its effect on transcription , 2006, Nucleic acids research.

[19]  Julie E Reed,et al.  Stabilisation of human telomeric quadruplex DNA and inhibition of telomerase by a platinum-phenanthroline complex. , 2007, Chemical communications.

[20]  B. Guyen,et al.  Synthesis, biophysical and biological evaluation of 3,6-bis-amidoacridines with extended 9-anilino substituents as potent G-quadruplex-binding telomerase inhibitors. , 2004, Bioorganic & medicinal chemistry letters.

[21]  Y-X Zeng,et al.  Inhibition of myc promoter and telomerase activity and induction of delayed apoptosis by SYUIQ-5, a novel G-quadruplex interactive agent in leukemia cells , 2007, Leukemia.

[22]  S. Neidle,et al.  Inhibition of human telomerase by a G-quadruplex-interactive compound. , 1997, Journal of medicinal chemistry.

[23]  S. Neidle,et al.  Highly prevalent putative quadruplex sequence motifs in human DNA , 2005, Nucleic acids research.

[24]  S. Maiti,et al.  Furan based cyclic oligopeptides selectively target G-quadruplex. , 2007, Journal of medicinal chemistry.

[25]  J. Mergny,et al.  Apoptosis related to telomere instability and cell cycle alterations in human glioma cells treated by new highly selective G-quadruplex ligands , 2005, Oncogene.

[26]  M. Blasco,et al.  Porphyrin-aminoquinoline conjugates as telomerase inhibitors. , 2003, Organic & biomolecular chemistry.

[27]  Dinshaw J. Patel,et al.  Human telomere, oncogenic promoter and 5′-UTR G-quadruplexes: diverse higher order DNA and RNA targets for cancer therapeutics , 2007, Nucleic acids research.

[28]  E. De Pauw,et al.  Interactions of cryptolepine and neocryptolepine with unusual DNA structures. , 2003, Biochimie.

[29]  S. Neidle,et al.  Stabilization of G-quadruplex DNA by highly selective ligands via click chemistry. , 2006, Journal of the American Chemical Society.

[30]  T. Hermann,et al.  Aggregation and G-quadruplex DNA-binding study of 6a,12a-diazadibenzo-[a,g]fluorenylium derivative. , 2004, Bioorganic & medicinal chemistry letters.

[31]  U. Klotz,et al.  Biopharmaceutical Characterization of the Telomerase Inhibitor BRACO19 , 2006, Pharmaceutical Research.

[32]  Vijay Gokhale,et al.  Design and synthesis of an expanded porphyrin that has selectivity for the c-MYC G-quadruplex structure. , 2005, Journal of the American Chemical Society.

[33]  J. Darnell,et al.  Fragile X Mental Retardation Protein Targets G Quartet mRNAs Important for Neuronal Function , 2001, Cell.

[34]  J. Mergny,et al.  Cell senescence and telomere shortening induced by a new series of specific G-quadruplex DNA ligands , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[35]  Michael Fry,et al.  Tetraplex DNA and its interacting proteins. , 2007, Frontiers in bioscience : a journal and virtual library.

[36]  A. Phan,et al.  Small-molecule interaction with a five-guanine-tract G-quadruplex structure from the human MYC promoter , 2005, Nature chemical biology.

[37]  S. Balasubramanian,et al.  G-quadruplex-specific peptide-hemicyanine ligands by partial combinatorial selection. , 2003, Journal of the American Chemical Society.

[38]  N. Maizels,et al.  Intracellular transcription of G-rich DNAs induces formation of G-loops, novel structures containing G4 DNA. , 2004, Genes & development.

[39]  N. Farrell,et al.  Cross-links of quadruplex structures from human telomeric DNA by dinuclear platinum complexes show the flexibility of both structures. , 2005, Biochemistry.

[40]  K. Shin‐ya,et al.  Telomestatin-induced stabilization of the human telomeric DNA quadruplex monitored by electrospray mass spectrometry. , 2003, Chemical communications.

[41]  T. Bryan,et al.  Physiological relevance of telomeric G‐quadruplex formation: a potential drug target , 2007, BioEssays : news and reviews in molecular, cellular and developmental biology.

[42]  Roger A. Jones,et al.  An intramolecular G-quadruplex structure with mixed parallel/antiparallel G-strands formed in the human BCL-2 promoter region in solution. , 2006, Journal of the American Chemical Society.

[43]  S. Balasubramanian,et al.  Tetramethylpyridiniumporphyrazines--a new class of G-quadruplex inducing and stabilising ligands. , 2006, Chemical communications.

[44]  R. Wheelhouse,et al.  Quadruplex-interactive agents as telomerase inhibitors: synthesis of porphyrins and structure-activity relationship for the inhibition of telomerase. , 2001, Journal of medicinal chemistry.

[45]  J. Mergny,et al.  Benzoindoloquinolines interact with DNA tetraplexes and inhibit telomerase. , 2002, Bioorganic & medicinal chemistry letters.

[46]  L. Kèlland,et al.  Targeting the Limitless Replicative Potential of Cancer: The Telomerase/Telomere Pathway , 2007, Clinical Cancer Research.

[47]  E. Pauw,et al.  Triplex and quadruplex DNA structures studied by electrospray mass spectrometry. , 2002, Rapid communications in mass spectrometry : RCM.

[48]  K. Shin‐ya,et al.  Telomerase inhibition, telomere shortening, cell growth suppression and induction of apoptosis by telomestatin in childhood neuroblastoma cells. , 2005, European journal of cancer.

[49]  S. Kerwin,et al.  The relationship between ligand aggregation and G-quadruplex DNA selectivity in a series of 3,4,9,10-perylenetetracarboxylic acid diimides. , 2002, Biochemistry.

[50]  Charles A Laughton,et al.  Pharmacodynamics of the G-Quadruplex-Stabilizing Telomerase Inhibitor 3,11-Difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium methosulfate (RHPS4) in Vitro: Activity in Human Tumor Cells Correlates with Telomere Length and Can Be Enhanced, or Antagonized, with Cytotoxic Agents , 2005, Molecular Pharmacology.

[51]  Laurence H. Hurley,et al.  DNA and its associated processes as targets for cancer therapy , 2002, Nature Reviews Cancer.

[52]  Christian Bailly,et al.  Targeting DNA with novel diphenylcarbazoles. , 2004, Biochemistry.

[53]  O. Fedoroff,et al.  Induction of Duplex to G-quadruplex Transition in the c-myc Promoter Region by a Small Molecule* , 2001, The Journal of Biological Chemistry.

[54]  Souvik Maiti,et al.  Hoechst 33258 binds to G-quadruplex in the promoter region of human c-myc. , 2003, Biochemical and biophysical research communications.

[55]  G. Parkinson,et al.  Structural basis for binding of porphyrin to human telomeres. , 2007, Biochemistry.

[56]  Stephen Neidle,et al.  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. , 2006, Journal of medicinal chemistry.

[57]  S. Neidle,et al.  1,4- and 2,6-disubstituted amidoanthracene-9,10-dione derivatives as inhibitors of human telomerase. , 1998, Journal of medicinal chemistry.

[58]  Stephen Neidle,et al.  The design of G-quadruplex ligands as telomerase inhibitors. , 2003, Mini reviews in medicinal chemistry.

[59]  N. Maizels,et al.  Specific interactions of distamycin with G-quadruplex DNA. , 2003, Nucleic acids research.

[60]  Jean-Louis Mergny,et al.  A New Steroid Derivative Stabilizes G-Quadruplexes and Induces Telomere Uncapping in Human Tumor Cells , 2007, Molecular Pharmacology.

[61]  S. Icli,et al.  Spectral properties and G-quadruplex DNA binding selectivities of a series of unsymmetrical perylene diimides , 2007 .

[62]  Stephen Neidle,et al.  A conserved quadruplex motif located in a transcription activation site of the human c-kit oncogene. , 2006, Biochemistry.

[63]  Christian Bailly,et al.  Tight Binding of the Antitumor Drug Ditercalinium to Quadruplex DNA , 2002, Chembiochem : a European journal of chemical biology.

[64]  S. Neidle,et al.  Natural and synthetic G-quadruplex interactive berberine derivatives. , 2006, Bioorganic & medicinal chemistry letters.

[65]  E. Gilson,et al.  Natural and pharmacological regulation of telomerase. , 2002, Nucleic acids research.

[66]  Stephen Neidle,et al.  Mechanism of acridine-based telomerase inhibition and telomere shortening. , 2007, Biochemical pharmacology.

[67]  Cheng-Chung Chang,et al.  Investigation of spectral conversion of d(TTAGGG)4 and d(TTAGGG)13 upon potassium titration by a G-quadruplex recognizer BMVC molecule , 2007, Nucleic acids research.

[68]  Laurence H. Hurley,et al.  Facilitation of a structural transition in the polypurine/polypyrimidine tract within the proximal promoter region of the human VEGF gene by the presence of potassium and G-quadruplex-interactive agents , 2005, Nucleic acids research.

[69]  Jinguo Huang,et al.  Cationic corrole derivatives: a new family of G-quadruplex inducing and stabilizing ligands. , 2007, Chemical communications.

[70]  D. Bednarski,et al.  Synthesis and testing of a triaza-cyclopenta[b]phenanthrene scaffold as a DNA binding agent. , 2006, Bioorganic & medicinal chemistry.

[71]  J. Mergny,et al.  Quadruplex ligands may act as molecular chaperones for tetramolecular quadruplex formation , 2007, Nucleic acids research.

[72]  Stephen Neidle,et al.  Chemical approaches to the discovery and development of cancer therapies , 2005, Nature Reviews Cancer.

[73]  S. Neidle,et al.  Structure-specific recognition of quadruplex DNA by organic cations: influence of shape, substituents and charge. , 2007, Biophysical chemistry.

[74]  G. Ortaggi,et al.  Specific interactions with intra- and intermolecular G-quadruplex DNA structures by hydrosoluble coronene derivatives: a new class of telomerase inhibitors. , 2007, Bioorganic & medicinal chemistry.

[75]  Ping Wang,et al.  A Phenol Quaternary Ammonium Porphyrin as a Potent Telomerase Inhibitor by Selective Interaction with Quadruplex DNA , 2006, Chembiochem : a European journal of chemical biology.

[76]  M. Blasco,et al.  A G-quadruplex ligand with 10000-fold selectivity over duplex DNA. , 2007, Journal of the American Chemical Society.

[77]  Roger A. Jones,et al.  Solution structure of the biologically relevant G-quadruplex element in the human c-MYC promoter. Implications for G-quadruplex stabilization. , 2005, Biochemistry.

[78]  Sarah W. Burge,et al.  Quadruplex DNA: sequence, topology and structure , 2006, Nucleic acids research.

[79]  J. Sessler,et al.  Cyclo[n]pyrroles: size and site-specific binding to G-quadruplexes. , 2006, Journal of the American Chemical Society.

[80]  C. Renner,et al.  Neomycin-capped aromatic platforms: quadruplex DNA recognition and telomerase inhibition. , 2006, Organic & biomolecular chemistry.

[81]  Daekyu Sun,et al.  Evidence for the presence of a guanine quadruplex forming region within a polypurine tract of the hypoxia inducible factor 1alpha promoter. , 2005, Biochemistry.

[82]  J. Mergny,et al.  Ethidium derivatives bind to G-quartets, inhibit telomerase and act as fluorescent probes for quadruplexes. , 2001, Nucleic acids research.

[83]  S. Neidle,et al.  Structure-based design of benzylamino-acridine compounds as G-quadruplex DNA telomere targeting agents. , 2007, Bioorganic & medicinal chemistry letters.

[84]  J. Brodbelt,et al.  Evaluation of binding of perylene diimide and benzannulated perylene diimide ligands to dna by electrospray ionization mass spectrometry , 2006, Journal of the American Society for Mass Spectrometry.

[85]  E. Raymond,et al.  Effects of cationic porphyrins as G-quadruplex interactive agents in human tumor cells. , 1999, Cancer research.

[86]  L. Hurley,et al.  Deconvoluting the structural and drug-recognition complexity of the G-quadruplex-forming region upstream of the bcl-2 P1 promoter. , 2006, Journal of the American Chemical Society.

[87]  A. Phan,et al.  DNA architecture: from G to Z. , 2006, Current opinion in structural biology.

[88]  Stephen Neidle,et al.  Putative DNA quadruplex formation within the human c-kit oncogene. , 2005, Journal of the American Chemical Society.

[89]  J. Lehn,et al.  Molecular Recognition of Anionic Substrates. Crystal Structures of the Supramolecular Inclusion Complexes of Terephthalate and Isophthalate Dianions with a Bis-intercaland Receptor Molecule , 1999 .

[90]  B. Pagano,et al.  Energetics of quadruplex-drug recognition in anticancer therapy. , 2007, Current cancer drug targets.

[91]  Jingli Yuan,et al.  A spectroscopic study on the interactions of porphyrin with G-quadruplex DNAs. , 2006, Biochemistry.

[92]  A. Chan,et al.  Stabilization of G-quadruplex DNA and down-regulation of oncogene c-myc by quindoline derivatives. , 2007, Journal of medicinal chemistry.

[93]  B. Dutrillaux,et al.  Preferential binding of a G-quadruplex ligand to human chromosome ends , 2005, Nucleic acids research.

[94]  L. Hurley,et al.  Biophysical studies of the c-MYC NHE III1 promoter: model quadruplex interactions with a cationic porphyrin. , 2007, Biophysical journal.

[95]  M. Teulade‐Fichou,et al.  FRET templated by G-quadruplex DNA: a specific ternary interaction using an original pair of donor/acceptor partners. , 2006, Journal of the American Chemical Society.

[96]  H. Kondo,et al.  Electrochemical telomerase assay with ferrocenylnaphthalene diimide as a tetraplex DNA-specific binder. , 2005, Analytical chemistry.

[97]  T. Randall Lee,et al.  The influence of pH on the G-quadruplex binding selectivity of perylene derivatives. , 2006, Bioorganic & medicinal chemistry letters.

[98]  M. Boxer,et al.  Tri-, tetra- and heptacyclic perylene analogues as new potential antineoplastic agents based on DNA telomerase inhibition. , 2007, Bioorganic & medicinal chemistry.

[99]  Patrick Mailliet,et al.  Stabilization of the c-myc gene promoter quadruplex by specific ligands' inhibitors of telomerase. , 2004, Biochemical and biophysical research communications.

[100]  D. V. Von Hoff,et al.  Design and synthesis of fluoroquinophenoxazines that interact with human telomeric G-quadruplexes and their biological effects. , 2001, Molecular cancer therapeutics.

[101]  I. Kuntz,et al.  Spectroscopic recognition of guanine dimeric hairpin quadruplexes by a carbocyanine dye. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[102]  N. Maizels,et al.  Dynamic roles for G4 DNA in the biology of eukaryotic cells , 2006, Nature Structural &Molecular Biology.

[103]  S. Neidle,et al.  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. , 2003, Molecular pharmacology.

[104]  E. De Pauw,et al.  Stabilization and structure of telomeric and c-myc region intramolecular G-quadruplexes: the role of central cations and small planar ligands. , 2007, Journal of the American Chemical Society.

[105]  S. Bombard,et al.  Platinum cross-linking of adenines and guanines on the quadruplex structures of the AG3(T2AG3)3 and (T2AG3)4 human telomere sequences in Na+ and K+ solutions. , 2003, Nucleic acids research.

[106]  M. Stevens,et al.  Antitumor polycyclic acridines. 7. Synthesis and biological properties of DNA affinic tetra- and pentacyclic acridines. , 2000, Journal of medicinal chemistry.

[107]  D. Bearss,et al.  Telomere inhibition and telomere disruption as processes for drug targeting. , 2003, Annual review of pharmacology and toxicology.

[108]  E. LaVoie,et al.  Synthesis and G-quadruplex stabilizing properties of a series of oxazole-containing macrocycles. , 2006, Bioorganic & medicinal chemistry letters.

[109]  R. Nagle,et al.  Mutations in the G-quadruplex silencer element and their relationship to c-MYC overexpression, NM23 repression, and therapeutic rescue. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[110]  K. Shin‐ya,et al.  Design and synthesis of telomestatin derivatives and their inhibitory activity of telomerase , 2006 .

[111]  R. Deng,et al.  Senescence and telomere shortening induced by novel potent G-quadruplex interactive agents, quindoline derivatives, in human cancer cell lines , 2006, Oncogene.

[112]  Cheng-Chung Chang,et al.  A fluorescent carbazole derivative: high sensitivity for quadruplex DNA. , 2003, Analytical chemistry.

[113]  L. Hurley,et al.  Formation of pseudosymmetrical G-quadruplex and i-motif structures in the proximal promoter region of the RET oncogene. , 2007, Journal of the American Chemical Society.

[114]  J. Chaires,et al.  Design, synthesis, and evaluation of novel biarylpyrimidines: a new class of ligand for unusual nucleic acid structures. , 2006, Journal of medicinal chemistry.

[115]  J. Chaires,et al.  Interaction of an Acridine Dimer with DNA Quadruplex Structures , 2001, Journal of biomolecular structure & dynamics.

[116]  J. Chaires,et al.  Sequence and structural selectivity of nucleic acid binding ligands. , 1999, Biochemistry.

[117]  S. Balasubramanian,et al.  Trisubstituted isoalloxazines as a new class of G-quadruplex binding ligands: small molecule regulation of c-kit oncogene expression. , 2007, Journal of the American Chemical Society.

[118]  Alastair I.H. Murchie,et al.  Retinoblastoma susceptibility genes contain 5' sequences with a high propensity to form guanine-tetrad structures , 1992, Nucleic Acids Res..

[119]  S. Neidle,et al.  A G-quadruplex-interactive potent small-molecule inhibitor of telomerase exhibiting in vitro and in vivo antitumor activity. , 2002, Molecular pharmacology.

[120]  V. Szalai,et al.  Parallel-stranded guanine quadruplex interactions with a copper cationic porphyrin. , 2004, Biochemistry.

[121]  Cooper Sj,et al.  Ultraviolet B Regulation of Transcription Factor Families: Roles of Nuclear Factor-kappa B (NF-κB) and Activator Protein-1 (AP-1) in UVB-Induced Skin Carcinogenesis , 2007 .

[122]  M. Searle,et al.  Drug recognition and stabilisation of the parallel-stranded DNA quadruplex d(TTAGGGT)4 containing the human telomeric repeat. , 2003, Journal of Molecular Biology.

[123]  N. Kallenbach,et al.  Interaction of the dye ethidium bromide with DNA containing guanine repeats. , 1992, Biochemistry.

[124]  Jim A. Thomas,et al.  Dinuclear monointercalating RuII complexes that display high affinity binding to duplex and quadruplex DNA. , 2006, Chemistry.

[125]  Stephen Neidle,et al.  The G-quadruplex-interactive molecule BRACO-19 inhibits tumor growth, consistent with telomere targeting and interference with telomerase function. , 2005, Cancer research.

[126]  Kazuo Shin-Ya,et al.  Telomestatin, a potent telomerase inhibitor that interacts quite specifically with the human telomeric intramolecular g-quadruplex. , 2002, Journal of the American Chemical Society.

[127]  A. Mehta,et al.  Structure of a quinobenzoxazine--G-quadruplex complex by REDOR NMR. , 2004, Biochemistry.

[128]  G. Ortaggi,et al.  Selective interactions of perylene derivatives having different side chains with inter- and intramolecular G-quadruplex DNA structures. A correlation with telomerase inhibition. , 2005, Bioorganic & medicinal chemistry letters.

[129]  Jan Postberg,et al.  Telomere end-binding proteins control the formation of G-quadruplex DNA structures in vivo , 2005, Nature Structural &Molecular Biology.

[130]  J. Mergny,et al.  Fluorescence Resonance Energy Transfer as a Probe for G‐Quartet Formation by a Telomeric Repeat , 2001, Chembiochem : a European journal of chemical biology.

[131]  J. Mergny,et al.  The importance of metal geometry in the recognition of G-quadruplex-DNA by metal-terpyridine complexes. , 2007, Organic & biomolecular chemistry.

[132]  L. Mayol,et al.  1 H-NMR study of the interaction of distamycin A and netropsin with the parallel stranded tetraplex [d(TGGGGT)]4 , 2001 .

[133]  Kevin B. Turner,et al.  End-stacking of copper cationic porphyrins on parallel-stranded guanine quadruplexes , 2007, JBIC Journal of Biological Inorganic Chemistry.

[134]  Jean-Louis Mergny,et al.  Targeting telomeres and telomerase. , 2008, Biochimie.

[135]  S Neidle,et al.  Molecular modeling studies on G-quadruplex complexes of telomerase inhibitors: structure-activity relationships. , 1999, Journal of medicinal chemistry.

[136]  P. Lou,et al.  Detection of quadruplex DNA structures in human telomeres by a fluorescent carbazole derivative. , 2004, Analytical chemistry.

[137]  M. Teulade‐Fichou,et al.  Development of a fluorescent intercalator displacement assay (G4-FID) for establishing quadruplex-DNA affinity and selectivity of putative ligands. , 2006, Bioorganic & medicinal chemistry letters.

[138]  J. Chaires,et al.  Biarylpyrimidines: a new class of ligand for high-order DNA recognition. , 2003, Chemical communications.

[139]  M. Blasco,et al.  Porphyrin Derivatives for Telomere Binding and Telomerase Inhibition , 2005, Chembiochem : a European journal of chemical biology.

[140]  A. R. Srinivasan,et al.  Defining the mode, energetics and specificity with which a macrocyclic hexaoxazole binds to human telomeric G-quadruplex DNA , 2007, Nucleic acids research.

[141]  Wei Li,et al.  Interactions of daidzin with intramolecular G‐quadruplex , 2006, FEBS letters.

[142]  M. Searle,et al.  Recognition and stabilization of quadruplex DNA by a potent new telomerase inhibitor: NMR studies of the 2:1 complex of a pentacyclic methylacridinium cation with d(TTAGGGT)4 , 2001 .

[143]  Jean-Louis Mergny,et al.  Affinity and selectivity of G4 ligands measured by FRET. , 2005, Nucleic acids symposium series.

[144]  Binh Nguyen,et al.  Biosensor-surface plasmon resonance: quantitative analysis of small molecule-nucleic acid interactions. , 2007, Methods.

[145]  Markus Kaiser,et al.  Fluorescence-based melting assays for studying quadruplex ligands. , 2007, Methods.

[146]  B. Saccà,et al.  DNA nanomachines and nanostructures involving quadruplexes. , 2006, Organic & biomolecular chemistry.

[147]  S. Neidle,et al.  2,7-Disubstituted amidofluorenone derivatives as inhibitors of human telomerase. , 1999, Journal of medicinal chemistry.

[148]  W. Wilson,et al.  Telomestatin and diseleno sapphyrin bind selectively to two different forms of the human telomeric G-quadruplex structure. , 2005, Journal of the American Chemical Society.

[149]  M. Salazar,et al.  Design and synthesis of the G-quadruplex-specific cleaving reagent perylene-EDTA.iron(II). , 2001, Journal of the American Chemical Society.

[150]  Shou-Dong Lee,et al.  A G-Quadruplex Ligand 3,3′-Diethyloxadicarbocyanine Iodide Induces Mitochondrion-Mediated Apoptosis But Not Decrease of Telomerase Activity in Nasopharyngeal Carcinoma NPC-TW01 Cells , 2004, Pharmaceutical Research.

[151]  S. Balasubramanian,et al.  Ligand-driven G-quadruplex conformational switching by using an unusual mode of interaction. , 2007, Angewandte Chemie.

[152]  Yalin Tang,et al.  Spectroscopic studies of the interaction between quercetin and G-quadruplex DNA. , 2006, Bioorganic & medicinal chemistry letters.

[153]  K. Shin‐ya,et al.  Total synthesis of (R)-telomestatin. , 2006, Organic letters.

[154]  Hamid Morjani,et al.  Telomestatin-induced Telomere Uncapping Is Modulated by POT1 through G-overhang Extension in HT1080 Human Tumor Cells* , 2006, Journal of Biological Chemistry.

[155]  P. Pečinka,et al.  DNA tetraplex formation in the control region of c-myc. , 1998, Nucleic acids research.

[156]  S. Kerwin,et al.  The aggregation and G-quadruplex DNA selectivity of charged 3,4,9,10-perylenetetracarboxylic acid diimides. , 2002, Bioorganic & medicinal chemistry letters.

[157]  J. Bremner,et al.  Selectivity of an indolyl berberine derivative for tetrameric G-quadruplex DNA. , 2007, Rapid communications in mass spectrometry : RCM.

[158]  Yasuhiko Yamamoto,et al.  Exogenous Ligand Binding Property of a Heme-DNA Coordination Complex , 2006 .

[159]  G. Ortaggi,et al.  New highly hydrosoluble and not self-aggregated perylene derivatives with three and four polar side-chains as G-quadruplex telomere targeting agents and telomerase inhibitors. , 2007, Bioorganic & medicinal chemistry letters.

[160]  R. Wheelhouse,et al.  Interactions of TMPyP4 and TMPyP2 with Quadruplex DNA. Structural Basis for the Differential Effects on Telomerase Inhibition , 1999 .

[161]  K. Shin‐ya,et al.  Telomestatin, a novel telomerase inhibitor from Streptomyces anulatus. , 2001, Journal of the American Chemical Society.

[162]  J. Trent,et al.  Intercalative G-Tetraplex Stabilization of Telomeric DNA by a Cationic Porphyrin1 , 1999 .

[163]  M. Stevens,et al.  Antitumor polycyclic acridines. 17. Synthesis and pharmaceutical profiles of pentacyclic acridinium salts designed to destabilize telomeric integrity. , 2005, Journal of medicinal chemistry.

[164]  L. Hurley,et al.  Binding of G-Quadruplex-interactive Agents to Distinct G-Quadruplexes Induces Different Biological Effects in MiaPaCa Cells , 2005, Nucleosides, nucleotides & nucleic acids.

[165]  R. Gartenhaus,et al.  Telomere uncapping by the G-quadruplex ligand RHPS4 inhibits clonogenic tumour cell growth in vitro and in vivo consistent with a cancer stem cell targeting mechanism , 2007, British Journal of Cancer.

[166]  D. Sun,et al.  G-quadruplex DNA binding by a series of carbocyanine dyes. , 2001, Bioorganic & medicinal chemistry letters.

[167]  K. Shin‐ya,et al.  G-Quadruplex stabilization by telomestatin induces TRF2 protein dissociation from telomeres and anaphase bridge formation accompanied by loss of the 3′ telomeric overhang in cancer cells , 2006, Oncogene.

[168]  P. Bolton,et al.  Fluorescent dyes specific for quadruplex DNA. , 1998, Nucleic acids research.

[169]  M. Rybczyńska,et al.  Spectroscopic study and G-quadruplex DNA binding affinity of two bioactive papaverine-derived ligands. , 2007, International journal of biological macromolecules.

[170]  K. Shin‐ya,et al.  Resistance to the Short Term Antiproliferative Activity of the G-quadruplex Ligand 12459 Is Associated with Telomerase Overexpression and Telomere Capping Alteration* , 2003, Journal of Biological Chemistry.

[171]  Jeremy K M Sanders,et al.  Synthesis and G-quadruplex binding studies of new 4-N-methylpyridinium porphyrins. , 2006, Organic & biomolecular chemistry.

[172]  J. Mergny,et al.  G‐Quadruplex Recognition by Quinacridines: a SAR, NMR, and Biological Study , 2007, ChemMedChem.

[173]  J. Mergny,et al.  Telomerase inhibitors based on quadruplex ligands selected by a fluorescence assay , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[174]  Jeffery T. Davis.  G-quartets 40 years later: from 5'-GMP to molecular biology and supramolecular chemistry. , 2004, Angewandte Chemie.

[175]  Shankar Balasubramanian,et al.  Prevalence of quadruplexes in the human genome , 2005, Nucleic acids research.

[176]  Roger A. Jones,et al.  NMR solution structure of the major G-quadruplex structure formed in the human BCL2 promoter region , 2006, Nucleic acids research.

[177]  J. Chaires,et al.  Preferential Binding of 3,3‘-Diethyloxadicarbocyanine to Triplex DNA , 2000 .

[178]  L. Hurley,et al.  The different biological effects of telomestatin and TMPyP4 can be attributed to their selectivity for interaction with intramolecular or intermolecular G-quadruplex structures. , 2003, Cancer research.

[179]  M. Fry,et al.  Formation and properties of hairpin and tetraplex structures of guanine-rich regulatory sequences of muscle-specific genes , 2005, Nucleic acids research.

[180]  S. Neidle,et al.  Human telomerase inhibition by regioisomeric disubstituted amidoanthracene-9,10-diones. , 1998, Journal of medicinal chemistry.

[181]  Shankar Balasubramanian,et al.  G-quadruplexes in promoters throughout the human genome , 2006, Nucleic acids research.

[182]  S. Balasubramanian,et al.  Single-molecule conformational analysis of G-quadruplex formation in the promoter DNA duplex of the proto-oncogene c-kit. , 2007, Journal of the American Chemical Society.

[183]  L. Loeb,et al.  The fragile X syndrome d(CGG)n nucleotide repeats form a stable tetrahelical structure. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[184]  G. Guy,et al.  BNIP-Sα induces cell rounding and apoptosis by displacing p50RhoGAP and facilitating RhoA activation via its unique motifs in the BNIP-2 and Cdc42GAP homology domain , 2006, Oncogene.

[185]  Carlo Leonetti,et al.  Telomere damage induced by the G-quadruplex ligand RHPS4 has an antitumor effect. , 2007, The Journal of clinical investigation.

[186]  Jinguo Huang,et al.  Quaternary Ammonium Zinc Phthalocyanine: Inhibiting Telomerase by Stabilizing G quadruplexes and Inducing G‐Quadruplex Structure Transition and Formation , 2007, Chembiochem : a European journal of chemical biology.

[187]  I Berger,et al.  In vitro generated antibodies specific for telomeric guanine-quadruplex DNA react with Stylonychia lemnae macronuclei , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[188]  K. Shin‐ya,et al.  Reevaluation of telomerase inhibition by quadruplex ligands and their mechanisms of action , 2007, Proceedings of the National Academy of Sciences.

[189]  C B Harley,et al.  Specific association of human telomerase activity with immortal cells and cancer. , 1994, Science.

[190]  Lin Ma,et al.  Synthesis and evaluation of quindoline derivatives as G-quadruplex inducing and stabilizing ligands and potential inhibitors of telomerase. , 2005, Journal of medicinal chemistry.

[191]  D. Bearss,et al.  Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[192]  M. Teulade‐Fichou,et al.  A platinum–quinacridine hybrid as a G-quadruplex ligand , 2007, JBIC Journal of Biological Inorganic Chemistry.

[193]  K. Shin‐ya,et al.  The G-quadruplex ligand telomestatin inhibits POT1 binding to telomeric sequences in vitro and induces GFP-POT1 dissociation from telomeres in human cells. , 2006, Cancer research.

[194]  Kwok‐yin Wong,et al.  9-Substituted berberine derivatives as G-quadruplex stabilizing ligands in telomeric DNA. , 2007, Bioorganic & medicinal chemistry.

[195]  Samer Khateb,et al.  The tetraplex (CGG)n destabilizing proteins hnRNP A2 and CBF-A enhance the in vivo translation of fragile X premutation mRNA , 2007, Nucleic acids research.

[196]  B. Meunier,et al.  Oxidative damage generated by an oxo-metalloporphyrin onto the human telomeric sequence. , 2000, Biochemistry.

[197]  S. Neidle,et al.  Structure of the first parallel DNA quadruplex-drug complex. , 2003, Journal of the American Chemical Society.

[198]  B. Guyen,et al.  Synthesis and evaluation of analogues of 10H-indolo[3,2-b]quinoline as G-quadruplex stabilising ligands and potential inhibitors of the enzyme telomerase. , 2004, Organic & biomolecular chemistry.

[199]  J. Mergny,et al.  Telomerase downregulation induced by the G-quadruplex ligand 12459 in A549 cells is mediated by hTERT RNA alternative splicing. , 2004, Nucleic acids research.

[200]  S. Bombard,et al.  GG sequence of DNA and the human telomeric sequence react with cis-diammine-diaquaplatinum at comparable rates. , 2007, Journal of inorganic biochemistry.

[201]  J. Zahm,et al.  Overexpression of Bcl-2 is associated with apoptotic resistance to the G-quadruplex ligand 12459 but is not sufficient to confer resistance to long-term senescence , 2005, Nucleic acids research.