Telomere maintenance as a target for anticancer drug discovery (original) (raw)

• Sahai, E. & Marshall, J. C. RHO-GTPases and cancer. Nature Rev. Cancer 2, 133–142 (2002).
  Article Google Scholar
• Pines, J. Four-dimensional control of the cell cycle. Nature Cell Biol. 1, E73–E79 (1999).
  Article CAS PubMed Google Scholar
• Blackburn, E. H. Switching and signaling at the telomere. Cell 106, 661–673 (2001).
  Article CAS PubMed Google Scholar
• McElligott, R. & Wellinger, R. J. The terminal DNA structure of mammalian chromosomes. EMBO J. 16, 3705–3714 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Huffman, K. E., Levene, S. D., Tesmer, V. M., Shay, J. W. & Wright, W. E. Telomere shortening is proportional to the size of the G-rich telomeric 3′-overhang. J. Biol. Chem. 275, 19719–19722 (2000).
  Article CAS PubMed Google Scholar
• Wright, W. E., Tesmer, V. M., Huffman, K. E., Levene, S. D. & Shay, J. W. Normal human chromosomes have long G-rich telomeric overhangs at one end. Genes Dev. 11, 2801–2809 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• van Steensel, B., Smogorzewska, A. & de Lange, T. TRF2 protects human telomeres from end-to-end fusions. Cell 92, 401–413 (1998).
  Article CAS PubMed Google Scholar
• Baumann, P. & Cech, T. R. POT1, the putative telomere end-binding protein in fission yeast and humans. Science 292, 1171–1175 (2001).Characterization of an end-capping protein, and investigation of its homology with other telomere-associated proteins.
  Article CAS PubMed Google Scholar
• Nakamura, T. M. et al. Telomerase catalytic subunit homologs from fission yeast and human. Science 277, 955–959 (1997).
  Article CAS PubMed Google Scholar
• Simonsson, T. G-quadruplex DNA structures — variations on a theme. Biol. Chem. 382, 621–628 (2001).
  Article CAS PubMed Google Scholar
• Kerwin, S. M. G-quadruplex DNA as a target for drug design. Curr. Pharm. Des. 6, 441–478 (2000).
  Article CAS PubMed Google Scholar
• van Steensel, B. & de Lange, T. Control of telomere length by the human telomeric protein TRF1. Nature 385, 740–743 (1997).
  Article CAS PubMed Google Scholar
• Kim, N. W. et al. Specific association of human telomerase activity with immortal cell and cancer. Science 266, 2011–2015 (1994). The key demonstration that a wide range of human cancers have a high proportion with elevated levels of expressed telomerase.
  Article CAS PubMed Google Scholar
• Greider, C. W. & Blackburn, E. H. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43, 405–413 (1985). The first characterization of the telomerase enzyme from any species.
  Article CAS PubMed Google Scholar
• Keith, W. N., Evans, T. R. & Glasspool, R. M. Telomerase and cancer: time to move from a promising target to a clinical reality. J. Pathol. 195, 404–414 (2001).
  Article CAS PubMed Google Scholar
• Bryan, T. M. & Cech, T. R. Telomerase and maintenance of chromosome ends. Curr. Opin. Cell Biol. 11, 318–324 (1999).
  Article CAS PubMed Google Scholar
• Feng, J. et al. The RNA component of human telomerase. Science 269, 1236–1241 (1995). Characterization of the RNA domain of human telomerase.
  Article CAS PubMed Google Scholar
• Chen, J. L., Blasco, M. A. & Greider, C. W. Secondary structure of vertebrate telomerase RNA. Cell 100, 503–514 (2000).
  Article CAS PubMed Google Scholar
• Meyerson, M. et al. hEST2, the putative human telomerase catalytic subunit gene, is upregulated in tumor cells and during immortalization. Cell 90, 785–795 (1997).
  Article CAS PubMed Google Scholar
• Griffith, J. D. et al. Mammalian telomeres end in a large duplex loop. Cell 97, 503–514 (1999). Visualization using electron microscopy, showing that telomeres can form a loop structure.
  Article CAS PubMed Google Scholar
• Stansel, R. M., de Lange, T. & Griffith, J. D. T-loop assembly in vitro involves binding of TRF2 near the 3′ telomeric overhang. EMBO J. 20, 5532–5540 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Li., B., Oestreich, S. & de Lange, T. Identification of human Rap1: implications for telomere evolution. Cell 101, 417–483 (2000).
  Google Scholar
• Smith, S., Giriat, I., Schmitt, A. & de Lange, T. Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. Science 282, 1484–1487 (1998).
  Article CAS PubMed Google Scholar
• Kaminker, P. G. et al. TANK2, a new TRF1-associated poly(ADP-ribose) polymerase, causes rapid induction of cell death upon overexpression. J. Biol. Chem. 276, 35891–35899 (2001).
  Article CAS PubMed Google Scholar
• Kim, S. H., Kaminker, P. & Campisi, J. TIN2, a new regulator of telomere length in human cells. Nature Genet. 23, 405–412 (1999).
  Article CAS PubMed Google Scholar
• Forsythe, H. L., Jarvis, J. L., Turner, J. W., Elmore, L. W. & Holt, S. E. Stable association of hsp90 and p23, but not hsp70, with active human telomerase. J. Biol. Chem. 276, 15571–15574 (2001).
  Article CAS PubMed Google Scholar
• Hsu, H. L. et al. Ku acts in a unique way at the mammalian telomere to prevent end joining. Genes Dev. 14, 2807–2812 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Wu, K. J. et al. Direct activation of TERT transcription by c-MYC. Nature Genet. 21, 220–224 (1999).
  Article CAS PubMed Google Scholar
• Karlseder, J., Broccoli, D., Dai, Y., Hardy, S. & de Lange, T. p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science 283, 1321–1325 (1999).
  Article CAS PubMed Google Scholar
• Simonsson, T. & Henriksson, M. c-myc Suppression in Burkitt's lymphoma cells. Biochem. Biophys. Res. Commun. 290, 11–15 (2002).
  Article CAS PubMed Google Scholar
• Rangan, A., Fedoroff, O. Y. & Hurley, L. H. Induction of duplex to G-quadruplex transition in the c-myc promoter region by a small molecule. J. Biol. Chem. 276, 4640–4646 (2001).
  Article CAS PubMed Google Scholar
• Hahn, W. C. et al. Creation of human tumour cells with defined genetic elements. Nature 400, 464–468 (1999).
  Article CAS PubMed Google Scholar
• Hahn, W. C. et al. Inhibition of telomerase limits the growth of human cancer cells. Nat Med 5, 1164–1170 (1999). Proof-of-principle experiments that show that inhibition of telomerase, using a dominant-negative mutant, results in telomere shortening and cellular senescence.
  Article CAS PubMed Google Scholar
• Shammas, M. A., Simmons, C. G., Corey, D. R. & Shmookler Reis, R. J. Telomerase inhibition by peptide nucleic acids reverses 'immortality' of transformed human cells. Oncogene 18, 6191–6200 (1999).
  Article CAS PubMed Google Scholar
• Herbert, B. S. et al. Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death. Proc. Natl Acad. Sci. USA 96, 14276–14281 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Bryan, T. M., Englezou, A., Dalla-Pozza, L., Dunham, M. A. & Reddel, R. R. Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. Nature Med. 3, 1271–1274 (1997).
  Article CAS PubMed Google Scholar
• Dunham, M. A., Neumann, A. A., Fasching, C. L. & Reddel, R. R. Telomere maintenance by recombination in human cells. Nature Genet. 26, 447–450 (2000).
  Article CAS PubMed Google Scholar
• Sun, H., Karow, J. K., Hickson, I. D. & Maizels, N. The Bloom's syndrome helicase unwinds G4 DNA. J. Biol. Chem. 273, 27587–27592 (1998).
  Article CAS PubMed Google Scholar
• Li, J. L. et al. Inhibition of the Bloom's and Werner's syndrome helicases by G-quadruplex interacting ligands. Biochemistry 40, 15194–15202 (2001).
  Article CAS PubMed Google Scholar
• Damm, K. et al. A highly selective telomerase inhibitor limiting human cancer cell proliferation. EMBO J. 20, 6958–6968 (2001). A detailed account of telomerase inhibition by a small molecule that acts as a catalytic inhibitor of the reverse transcriptase active site, including demonstration of telomere shortening and an antitumour effect.
  Article CAS PubMed PubMed Central Google Scholar
• Pascolo, E. et al. Mechanism of human telomerase inhibition by BIBR1532, a synthetic, non-nucleosidic drug candidate. J. Biol. Chem. 19 Feb 2002 [e-pub ahead of print].
• Hamilton, S. E. et al. Identification of determinants for inhibitor binding within the RNA active site of human telomerase using PNA scanning. Biochemistry 36, 11873–11880 (1997).
  Article CAS PubMed Google Scholar
• Pitts, A. E. & Corey, D. R. Inhibition of human telomerase by 2′-_O_-methyl-RNA. Proc. Natl Acad. Sci. USA 95, 11549–11554 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Elayadi, A. N., Demieville, A., Wancewicz, E. V., Monia, B. P. & Corey, D. R. Inhibition of telomerase by 2′-_O_-(2-methoxyethyl) RNA oligomers: effect of length, phosphorothioate substitution and time inside cells. Nucleic Acids Res. 29, 1683–1689 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Zahler, A. M., Williamson, J. R., Cech, T. R. & Prescott, D. M. Inhibition of telomerase by G-quartet DNA structures. Nature 350, 718–720 (1991).
  Article CAS PubMed Google Scholar
• Han, H. & Hurley, L. H. G-quadruplex DNA: a potential target for anti-cancer drug design. Trends Pharmacol. Sci. 21, 136–142 (2000).
  Article CAS PubMed Google Scholar
• Mergny, J. L. & Helene, C. G-quadruplex DNA: a target for drug design. Nature Med. 12, 1366–1367 (1998).
  Article Google Scholar
• Koeppel, F. et al. Ethidium derivatives bind to G-quartets, inhibit telomerase and act as fluorescent probes for quadruplexes. Nucleic Acids Res. 29, 1087–1096 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Read, M. et al. Structure-based design of selective and potent G quadruplex-mediated telomerase inhibitors. Proc. Natl Acad. Sci. USA 98, 4844–4849 (2001).Rational design of telomerase inhibitors has produced molecules with nanomolar potency, based on molecular-modelling studies using native quadruplex structures.
  Article CAS PubMed PubMed Central Google Scholar
• Mergny, J. L. et al. Telomerase inhibitors based on quadruplex ligands selected by a fluorescence assay. Proc. Natl Acad. Sci. USA 98, 3062–3067 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Mergny, J. L. & Maurizot, J. C. Fluorescence resonance energy transfer as a probe for G-quartet formation by a telomeric repeat. ChemBioChem 2, 124–132 (2001).
  Article CAS PubMed Google Scholar
• McEachern, M. J., Lyer, S., Fulton, T. B. & Blackburn, E. H. Telomere fusions caused by mutating the terminal region of telomeric DNA. Proc. Natl Acad. Sci. USA 97, 11409–11414 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Gowan, S. M. et al. A G-quadruplex-interactive potent small molecule inhibitor of telomerase exhibiting in vitro and in vivo antitumor activity. Mol. Pharmacol. (in the press).
• Hemann, M. T., Strong, M. A., Hao, L. Y. & Greider, C. W. The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Cell 107, 67–77 (2001).
  Article CAS PubMed Google Scholar
• Guo, Q., Lu, M., Marky, L. A. & Kallenbach, N. R. Interaction of the dye ethidium bromide with DNA containing guanine repeats. Biochemistry 31, 2451–2455 (1992).
  Article CAS PubMed Google Scholar
• Sun, D. et al. Inhibition of human telomerase by a G-quadruplex-interactive compound. J. Med. Chem. 40, 2113-2116 (1997). The first demonstration of telomerase inhibition by a quadruplex-interactive molecule.
• Izbicka, E. et al. Effects of cationic porphyrins as G-quadruplex interactive agents in human tumor cells. Cancer Res. 59, 639–644 (1999).
  CAS PubMed Google Scholar
• Shi, D. F., Wheelhouse, R. T., Sun, D. & Hurley, L. H. Quadruplex-interactive agents as telomerase inhibitors: synthesis of porphyrins and structure-activity relationship for the inhibition of telomerase. J. Med. Chem. 44, 4509–4523 (2001).
  Article CAS PubMed Google Scholar
• Wheelhouse, R. T., Sun, D., Han, H., Han, F. X. & Hurley, L. H. Cationic porphyrins as telomerase inhibitors: the interaction of tetra-(_N_-methyl-4-pyridyl)porphine with quadruplex DNA. J. Am. Chem. Soc. 120, 3261–3262 (1998).
  Article CAS Google Scholar
• Gowan, S. M., Heald, R., Stevens, M. F. & Kelland, L. R. Potent inhibition of telomerase by small-molecule pentacyclic acridines capable of interacting with G-quadruplexes. Mol. Pharmacol. 60, 981–988 (2001). A novel quadruplex-binding telomerase inhibitor that produces senescence in long-term cell culture.
  Article CAS PubMed Google Scholar
• Wang, Y. & Patel, D. J. Solution structure of the human telomeric repeat d[AG3(T2AG3)3] G-tetraplex. Structure 1, 263–282 (1993).
  Article CAS PubMed Google Scholar
• Harrison, R. J., Gowan, S. M., Kelland, L. R. & Neidle, S. Human telomerase inhibition by substituted acridine derivatives. Bioorg. Med. Chem. Lett. 9, 2463–2468 (1999).
  Article CAS PubMed Google Scholar
• Han, H., Cliff, C. L. & Hurley, L. H. Accelerated assembly of G-quadruplex structures by a small molecule. Biochemistry 38, 6981–6986 (1999).
  Article CAS PubMed Google Scholar
• Fedoroff, O. Y. et al. NMR-based model of a telomerase-inhibiting compound bound to G-quadruplex DNA. Biochemistry 37, 12367–12374 (1998).
  Article CAS PubMed Google Scholar
• Kerwin, S. M., Chen, G., Kern, J. T. & Thomas, P. W. Perylene diimide G-quadruplex DNA binding selectivity is mediated by ligand aggregation. Bioorg. Med. Chem. Lett. 12, 447–450 (2002).
  Article CAS PubMed Google Scholar
• Tuntiwechapikul, W. & Salazar, M. Cleavage of telomeric G-quadruplex DNA with perylene-EDTA*Fe(II). Biochemistry 40, 13652–13658 (2001).
  Article CAS PubMed Google Scholar
• Chen, Q., Kuntz, I. D. & Shafer, R. H. Spectroscopic recognition of guanine dimeric hairpin quadruplexes by a carbocyanine dye. Proc. Natl Acad. Sci. USA 93, 2635–2639 (1996). The use of virtual library screening to find a quadruplex-binding molecule.
  Article CAS PubMed PubMed Central Google Scholar
• Kerwin, S. M. et al. G-quadruplex binding by a series of carbocyanine dyes. Bioorg. Med. Chem. Lett. 11, 2411–2414 (2001).
  Article CAS PubMed Google Scholar
• Riou, J. F. et al. Cell senescence and telomere shortening induced by a new series of specific G-quadruplex DNA ligands. Proc. Natl Acad. Sci. USA 99, 2672–2677 (2002). Demonstration that quadruplex-interactive telomerase inhibitors can produce telomere shortening in cells.
  Article CAS PubMed PubMed Central Google Scholar
• Shin-ya, K. et al. Telomestatin, a novel telomerase inhibitor from Streptomyces anulatus. J. Am. Chem. Soc. 123, 1262–1263 (2001).
  Article CAS PubMed Google Scholar
• Kim, M. Y. et al. Telomestatin, a potent telomerase inhibitor that interacts quite specifically with the human telomeric intramolecular G-quadruplex. J. Am. Chem. Soc. 124, 2098–2099 (2002).
  Article CAS PubMed Google Scholar
• Buchdunger, E., Matter, A. & Druker, B. J. Bcr–Abl inhibition as a modality of CML therapeutics. Biochim. Biophys. Acta. 1551, M11–M18 (2001).
  CAS PubMed Google Scholar
• Sun, D., Hurley, L. H. & Von Hoff, D. D. Telomerase assay using biotinylated-primer extension and magnetic seperation of the products. Biotechniques 25, 1046–1051 (1998).
  Article CAS PubMed Google Scholar
• Perry, P. J. et al. 2,7-disubstituted amidofluorenone derivatives as inhibitors of human telomerase. J. Med. Chem. 42, 2679–2684 (1999).
  Article CAS PubMed Google Scholar
• Perry, P. J. et al. Human telomerase inhibition by regioisomeric disubstituted amidoanthracene-9,10-diones. J. Med. Chem. 41, 4873–4884 (1998).
  Article CAS PubMed Google Scholar
• Read, M. A. & Neidle, S. Structural characterization of a guanine-quadruplex ligand complex. Biochemistry 39, 13422–13432 (2000).
  Article CAS PubMed Google Scholar
• Gavathiotis, E., Heald, R. A., Stevens, F. G. & Searle, M. S. 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 . Angew. Chem. Int. Ed. 40, 4749–4751 (2001). An NMR study of quadruplex binding to a novel potent telomerase inhibitor, which demonstrates stacking onto the ends of the quadruplex.
  Article CAS Google Scholar
• Han, H., Langley, D. R., Rangan, A. & Hurley, L. H. Selective interactions of cationic porphyrins with G-quadruplex structures. J. Am. Chem. Soc. 123, 8902–8913 (2001).
  Article CAS PubMed Google Scholar
• Read, M. A. et al. Molecular modeling studies on G-quadruplex complexes of telomerase inhibitors: structure–activity relationships. J. Med. Chem. 42, 4538–4546 (1999).
  Article CAS PubMed Google Scholar
• Bearss, D. J., Hurley, L. H. & Von Hoff, D. D. Telomere maintenance mechanisms as a target for drug development. Oncogene 19, 6632–6641 (2000).
  Article CAS PubMed Google Scholar