Molecular modeling studies on G-quadruplex complexes of telomerase inhibitors: Structure-activity relationships

Journal of Medicinal Chemistry

Volumn 42, Issue 22, 1999, Pages 4538-4546

  Read, Martin A ^a   Wood, Alexis A ^a   Harrison, John R ^a   Gowan, Sharon M ^a   Kelland, Lloyd R ^a   Dosanjh, Harvinder S ^a   Neidle, Stephen ^a  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ENZYME INHIBITOR; TELOMERASE;

ARTICLE; BINDING AFFINITY; COMPLEX FORMATION; ENZYME INHIBITION; MOLECULAR MODEL; MOLECULAR STABILITY; STRUCTURE ACTIVITY RELATION;

ACRIDINES; ANTHRAQUINONES; ANTINEOPLASTIC AGENTS; CALORIMETRY; DNA; ENZYME INHIBITORS; HUMANS; MODELS, MOLECULAR; STRUCTURE-ACTIVITY RELATIONSHIP; TELOMERASE; TELOMERE;

EID: 0033524027     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm990287e     Document Type: Article

References (47)

1. Blackburn, E. H. Structure and function of telomeres. Nature 1991, 350, 569-573.
2. n among vertebrates. Proc. Natl. Acad. Sci. U.S.A. 1989, 86, 7049-7053.
3. Harley, C. B.; Futcher, A. B.; Greider, C. W. Telomeres Shorten During Aging of Human Fibroblasts. Nature 1990, 345, 458-460.
4. (b) Allsopp, R. C.; Harley, C. B. Evidence for a Critical Telomere Length in Senescent Human Fibroblasts. Exp. Cell Res. 1995, 219, 130-136.
5. Kim, N. W.; Piatyszek, M. A.; Prowse, K. R.; Harley, C. B.; West, M. D.; Ho, P. L. C.; Coviello, G. M.; Wright, W. E.; Weinrich, R. L.; Shay, J. W. Specific Association of Human Telomerase Activity with Immortal Cells and Cancer. Science 1994, 266, 2011-2015.
6. (b) Counter, C. M.; Hirte, H. W.; Bacchetti, S.; Harley, C. B. Telomerase Activity in Human Ovarian Carcinoma. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 2900-2904.
7. (c) Tang, R.; Cheng, A.-J.; Wang, J.-Y.; Wang, T.-C. V. Close Correlation between Telomerase Expression and Adenomatous Polyp Progression in Multistep Colorectal Carcinogenesis. Cancer Res. 1998, 58, 4052-4054.
8. (d) Hoos, A.; Hepp, H. H.; Kaul, S.; Ahlert, T.; Bastert, G.; Wallwiener, D. Telomerase Activity Correlates with Tumor Aggressiveness and Reflects Therapy Effect in Breast Cancer. Int. J. Cancer 1998, 79, 8-12.
9. (e) Sano, T.; Asai, A.; Fujimaki, T.; Kirino, T. Telomerase Activity in 144 Brain Tumours. Br. J. Cancer 1998, 77, 1633-1637.
10. Bodnar, A. G.; Ouellette, M.; Frolkis, M.; Holt, S. E.; Chiu, C. P.; Morin, G. B.; Harley, C. B.; Shay, J. W.; Lichtsteiner, S.; Wright, W. E. Extension of Life-span by Introduction of Telomerase into Normal Human Cells. Science 1998, 279, 349-352.
11. (b) Niida, H.; Matsumoto, T.; Satoh, H.; Shiwa, M.; Tokutake, Y.; Furuichi, Y.; Shinkai, Y. Severe Growth Defect in Mouse Cells Lacking the Telomerase RNA Component. Nature Genet. 1998, 19, 203-206.
12. (c) Blasco, M. A.; Lee, H.-W.; Hande, M. P.; Samper, E.; Lansdorp, P. M.; DePinho, R. A.; Greider, C. W. Telomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA. Cell 1997, 91, 25-34.
13. (d) Lee, H.-W.; Blasco, M. A.; Gottlieb, G. J.; Horner, J. W.; Greider, C. W.; DePinho, R. A. Essential Role of Mouse Telomerase in Highly Proliferative Organs. Nature 1998, 392, 569-574.
14. Greider, C. W. Telomerase Activation. One Step on the Road to Cancer? Trends in Genetics 1999, 15, 109-112.
15. (b) Zhu, J.; Wang, H.; Bishop, J. M.; Blackburn, E. H. Telomerase Extends the Life-span of Virus-transformed Human Cells without Net Telomere Lengthening. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 3723-3728.
16. (c) Counter, C. M.; Hahn, W. C.; Wei, W.; Caddle, S. D.; Beijersbergen, R. L.; Lansdorp, P. M.; Sedivy, J. M.; Weinberg, R. A. Dissociation among in vitro Telomerase Activity, Telomere Maintenance and Cellular Immortalization. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 14723-14728.
17. (d) Rudolph, K. L.; Chang, S.; Lee, H.-W.; Blasko, M.; Gottlieb, G. J.; Greider, C.; DePinho, R. A. Longevity, Stress Response and Cancer in Aging Telomerase-Deficient Mice. Cell 1999, 96, 701-712.
18. Perry, P. J.; Kelland, L. R. Telomeres and Telomerase: Targets for Cancer Chemotherapy. Exp. Opin. Ther. Patents 1998, 8, 1567-1586.
19. (b) Raymond, E.; Sun, D.; Chen, S.-F.; Windle, B.; von Hoff, D. D. Agents that Target Telomerase and Telomeres. Curr. Opin. Biotech. 1996, 7, 583-591.
20. (c) Pitts, A. E.; Corey, D. R. The Telomerase Challenge - an Unusual Problem in Drug Discovery. Drug Discovery Today 1999, 4, 155-161.
21. Hamilton, S. E.; Pitts, A. E.; Katipally, R. R.; Jia, X.; Rutter, J. P.; Davies, B. A.; Shay, J. W.; Wright, W. E.; Corey, D. R. Identification of Determinants for Inhibitor Binding within the RNA Active Site of Human Telomerase Using PNA Scanning. Biochemistry 1997, 36, 11873-11880.
22. (b) Kondo, S.; Kondo, Y.; Li, G.; Silverman, R. H.; Cowell, J. K. Targeted Therapy of Human Malignant Glioma in a Mouse Model by 2-5A Antisense Directed Against Telomerase RNA. Oncogene 1998, 16, 3323-3330.
23. Bisoffi, M.; Chakerian, A. E.; Fore, M. L.; Bryant, J. E.; Hernandez, J. P.; Moyzis, R. K; Griffith, J. K. Inhibition of Human Telomerase by a Retrovirus Expressing Telomeric Antisense RNA Eur. J. Cancer 1998, 34, 1242-1249.
24. Glukhov, A. I.; Zimnik, O. V.; Gordeev, S. A.; Severin, S. E. Inhibition of Telomerase Activity of Melanoma Cells in Vitro by Antisense Oligonucleotides. Biochem. Biophys. Res. Commun. 1998, 248, 368-371.
25. (e) Harrison, J. G.; Frier, C.; Laurant, R.; Dennis, R.; Raney, K. D.; Balasubramanian, S. Inhibition of human Telomerase by PNA-cationic Peptide Conjugates. Bioorg. Med. Chem. Lett. 1999, 9, 1273-1278.
26. Williamson, J. R. G-quartet structures in telomeric DNA. Annu. Rev. Biophys. Biomol. Struct. 1994, 23, 703-730.
27. Zahler, A. M.; Williamson, J. R.; Cech, T. R.; Prescott, D. M. Inhibition of Telomerase by G-quartet DNA Structures. Nature 1991, 350, 718-720.
28. Fletcher, T. M.; Sun, D.; Salazar, M.; Hurley, L. H. Effect of DNA Secondary Structure on Human Telomerase Activity. Biochemistry 1998, 37, 5536-5541.
29. (b) Sun, D.; Lopez-Guajardo, C. C.; Quada, J.; Hurley, L. H.; Von Hoff, D. D. Regulation of Catalytic Activity and Processivity of Human telomerase. Biochemistry 1999, 38, 4037-4044.
30. Marathias, V. M.; Bolton, P. H. Determinants of DNA Quadruplex Structural Type: Sequence and Potassium Binding. Biochemistry 1999, 38, 4355-4364.
31. Mergny, J.-L.; Hélène, C. G-Quadruplex DNA: a Target for Drug Design. Nature Med. 1998, 4, 1366-1367.
32. Sun, D.; Thompson, B.; Cathers, B. E.; Salazar, M.; Kerwin, S. M.; Trent, J. O.; Jenkins, T. C.; Neidle, S.; Hurley, L. H. Inhibition of Human Telomerase by a G-Quadruplex-Interactive Compound. J. Med. Chem. 1997, 40, 2113-2116.
33. (b) Perry, P. J.; Gowan, S. M.; Reszka, A. P.; Polucci, P.; Jenkins, T. C.; Kelland, L. R.; Neidle, S. 1,4-and 2,6-Disubstituted Amidoanthracene-9,10-dione Derivatives as Inhibitors of Human Telomerase. J. Med. Chem. 1998, 41, 3253-3260.
34. Perry, P. J.; Reszka, A. P.; Wood, A. A.; Read, M. A.; Gowan, S. M.; Dosanjh, H. S.; Trent, J. O.; Jenkins, T. C.; Kelland, L. R.; Neidle, S. Human Telomerase Inhibition by Regioisomeric Disubstituted Amidoanthracene-9,10-diones. J. Med. Chem. 1998, 41, 4873-4884.
35. Agbandje, M.; Jenkins, T. C.; Mckenna, R.; Reszka, A. P.; Neidle, S. Anthracene-9,10-diones as Potential Anticancer Agents. Synthesis, DNA Binding and Biological Studies on a Series of 2,6-Disubstituted Derivatives. J. Med. Chem. 1992, 35, 1418-1429.
36. Wheelhouse, R.; 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. 1998, 120, 3261-3262.
37. (b) Han, F. X.; Wheelhouse, R. T.; Hurley, L. H. Interactions of TMPyP4 and TMPyP2 with Quadruplex DNA. Structural Basis for the Differential Effects on Telomerase Inhibition. J. Am. Chem. Soc. 1999, 121, 3561-3570.
38. Federoff, O. V.; Salazar, M.; Han, H.; Chemeris, V. V.; Kerwin, S. M.; Hurley, L. H. NMR-Based Model of a Telomerase-Inhibiting Compound Bound to G-Quadruplex DNA. Biochemistry 1998, 37, 12367-12374.
39. 3] G-Tetraplex. Structure 1993, 1, 263-282.
40. Perry, P. J.; Read, M. A.; Davies, R. T.; Gowan, S. M.; Reszka, A. P.; Wood, A. A.; Kelland, L. R.; Neidle, S. 2,7-Disubstituted Amidofluorenone Derivatives as Inhibitors of Human Telomerase. J. Med. Chem. 1999, 42, 2679-2684.
41. Harrison, R. J.; Gowan, S. M.; Kelland, L. R.; Neidle, S. Human Telomerase Inhibition by Substituted Acridine Derivatives. Bioorg. Med. Chem. Lett., in press.
42. Åqvist, J.; Medina, C.; Samuuelsson, J.-E. A New Method for Predicting Binding Affinities in Computer-aided Drug Design. Protein Eng. 1994, 7, 385-391.
43. Luty, B. A.; Wasserman, Z. R.; Stouten, P. F. W.; Hodge, C. N.; Zacharias, M.; McCammon, J. A. A Molecular Mechanics/Grid Method for Evaluation of Ligand-Receptor Interactions. J. Comput. Chem. 1995, 16, 454-464.
44. Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds. John Wiley: New York, 1994, pp 765-767.
45. Han, H.; Hurley, L. H.; Salazar, M. A DNA Polymerase Stop Assay for G-Quadruplex-Interactive Compounds. Nucleic Acids Res. 1999, 27, 537-542.
46. INSIGHTII Modelling Environment. Molecular Simulations Inc.: San Diego, 1999.
47. Phillips, K.; Dauter, Z.; Murchie, A. I. H.; Lilley, D. M. J.; Luisi, B. The Crystal Structure of a Parallel-stranded Guanine Tetraplex at 0.95 Angstrom Resolution. J. Mol. Biol. 1997, 273, 171-182.