Evaluation of the interaction between long telomeric DNA and macrocyclic hexaoxazole (6OTD) dimer of a G-quadruplex ligand

Molecules

Volumn 18, Issue 4, 2013, Pages 4328-4341

  Iida, Keisuke ^a   Majima, Satoki ^a   Nakamura, Takahiro ^a   Seimiya, Hiroyuki ^b   Nagasawa, Kazuo ^a  

^a TOKYO UNIVERSITY OF AGRICULTURE AND TECHNOLOGY   (Japan)

^b CANCER CHEMOTHERAPY CENTER   (Japan)

Author keywords

G quadruplex; Macrocycles; Oxazole; Telomere; Telomestatin

Indexed keywords

DNA; GUANINE QUADRUPLEX; LIGAND; MACROCYCLIC COMPOUND; OXAZOLE DERIVATIVE; TELOMERASE; TELOMESTATIN;

ARTICLE; CHEMISTRY; DRUG ANTAGONISM; HUMAN; IC 50; SPECTROSCOPY; SYNTHESIS; TELOMERE; TUMOR CELL LINE;

CELL LINE, TUMOR; DNA; G-QUADRUPLEXES; HUMANS; INHIBITORY CONCENTRATION 50; LIGANDS; MACROCYCLIC COMPOUNDS; OXAZOLES; SPECTRUM ANALYSIS; TELOMERASE; TELOMERE;

EID: 84876759639     PISSN: None     EISSN: 14203049     Source Type: Journal    
DOI: 10.3390/molecules18044328     Document Type: Article

References (57)

1. Blackburn, E.H. Switching and Signaling at the Telomere. Cell 2001, 106, 661-673.
2. Hemann, M.T.; Greider, C.W. G-strand overhangs on telomeres in telomerase-deficient mouse cells. Nucleic Acids Res. 1999, 27, 3964-3969.
3. de Lange, T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 2005, 19, 2100-2010.
4. de Lange, T. How Shelterin solves the telomere end-protection problem. Cold Spring Harbor Symp. Quant. Biol. 2010, 75, 167-177.
5. Tsai, Y.C.; Qi, H.; Liu, L.F. Protection of DNA Ends by Telomeric 3' G-Tail Sequences. J. Biol. Chem. 2007, 282, 18786-18792.
6. Davis, J.T. G-Quartets 40 years later: From 5'-GMP to molecular biology and supramolecular chemistry. Angew. Chem. Int. Ed. 2004, 43, 668-698.
7. Patel, D.J.; Phan, A.T.; Kuryavyi, V. Human telomere, oncogenic promoter and 5'-UTR G-quadruplexes: Diverse higher order DNA and RNA targets for cancer therapeutics. Nucleic Acids Res. 2007, 35, 7429-7455.
8. Neidle, S.; Parkinson, G.N. Quadruplex DNA crystal structures and drug. Biochimie 2008, 90, 1184-1196.
9. Phan, A.T. Human telomeric G-quadruplex: Structures of DNA and RNA sequences. FEBS J. 2010, 277, 1107-1017.
10. Kim, N.W.; Piatyszek, M.A.; Prowse, K.R.; Harley, C.B.; West, M.D.; Ho, P.L.; Coviello, G.M.; Wright, W.E.; Weinrich, S.L.; Shay, J.W. Specific association of human telomerase activity with immortal cells and cancer. Science 1994, 266, 2011-2015.
11. Shay, J.W.; Wright, W.E. Telomerase therapeutics for cancer: challenges and new directions. Nat. Rev. Drug Discov. 2006, 5, 577-584.
12. 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.
13. Fumagalli, M.; Rossiello, F.; Clerici, M.; Barozzi, S.; Cittaro, D.; Kaplunov, J.M.; Bucci, G.; Dobreva, M.; Matti, V.; Beausejour, C.M.; et al. Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation. Nat. Cell Biol. 2012, 14, 335-365.
14. Neidle, S. Human telomeric G-quadruplex: The current status of telomeric G-quadruplexes as therapeutic targets in human cancer. FEBS J. 2010, 277, 1118-1125.
15. Monchaud, D.; Teulade-Fichou, M.-P. A hitchhiker's guide to G-quadruplex ligands. Org. Biomol. Chem. 2008, 6, 627-636
16. Ou, T.M.; Lu, Y.J.; Tan, J.H.; Huang, Z.S., Wong, K.Y.; Gu, L.Q. G-Quadruplexes: Targets in Anticancer Drug Design. ChemMedChem 2008, 3, 690-713
17. Shin-ya, K.; Wierzba, K.; Matsuo, K.; Ohtani, T.; Yamada, Y.; Furihata, K.; Hayakawa, Y.; Seto, H. Telomestatin, a Novel Telomerase Inhibitor from Streptomyces anulatus. J. Am. Chem. Soc. 2001, 123, 1262-1263.
18. Kim, M.Y.; Vankayalapati, H.; Shin-Ya, K.; Wierzba, K.; Hurley, L.H. Telomestatin, a Potent Telomerase Inhibitor That Interacts Quite Specifically with the Human Telomeric Intramolecular G-Quadruplex. J. Am. Chem. Soc. 2002, 124, 2098-2099.
19. Kim, M.Y.; Gleason-Guzman, M.; Izbicka, E.; Nishioka, D.; Hurley, L.H. The different biological effects of telomestatin and TMPyP4 can be attributed to their selectivity for interaction with intramolecular or intermolecular G-Quadruplex structures. Cancer Res. 2003, 63, 3247-3256.
20. Rosu, F.; Gabelica, V.; Shin-ya, K.; Pauw, E.D. Telomestatin-induced stabilization of the human telomeric DNA quadruplex monitored by electrospray mass spectrometry Chem. Commun. 2003, 2702-2703.
21. Rezler, E.M.; Seenisamy, J.; Bashyam, S.; Kim, M.Y.; White, E.; Wilson, W.D.; Hurley, L.H. Telomestatin and Diseleno Sapphyrin Bind Selectively to Two Different Forms of the Human Telomeric G-Quadruplex Structure. J. Am. Chem. Soc. 2005, 127, 9439-9447.
22. Doi, T.; Shibata, K.; Yoshida, M.; Takagi, M.; Tera, M.; Nagasawa, K.; Shin-ya, K.; Takahashi, T. (S)-Stereoisomer of telomestatin as a potent G-quadruplex binder and telomerase inhibitor. Org. Biomol. Chem. 2011, 9, 387-393.
23. Minhas, G.S.; Plich, D.S.; Kerrigan, J.E.; LaVoie, E.J.; Rice, J.E. Synthesis and G-quadruplex stabilizing properties of a series of oxazole-containing macrocycles. Bioorg. Med. Chem. Lett. 2006, 16, 3891-3895.
24. Barbieri, C.M.; Srinivasan, A.R.; Rzuczek, S.G.; Rice, J.E.; LaVoie, E.J.; Pilch, D.S. Defining the mode, energetics and specificity with which a macrocyclic hexaoxazole binds to human telomeric G-quadruplex DNA. Nucleic Acids Res. 2007, 35, 3272-3286.
25. Rzuczek, S.G.; Pilch, D.S.; LaVoie, E.J.; Rice, J.E. Lysinyl macrocyclic hexaoxazoles: Synthesis and selective G-quadruplex stabilizing properties. Bioorg. Med. Chem. Lett. 2008, 18, 913-917.
26. Satyanarayana, M.; Rzuczek, S.G.; LaVoie, E.J.; Pilch, D.S.; Liu, A.; Liu, L.F.; Rice, J.E. Ring-closing metathesis for the synthesis of a highly G-quadruplex selective macrocyclic hexaoxazole having enhanced cytotoxic potency Bioorg. Med. Chem. Lett. 2008, 18, 3802-3804.
27. Pilch, D.S.; Barbieri, C.M.; Rzuczek, S.G.; LaVoie, E.J.; Rice, J.E. Targeting human telomeric G-quadruplex DNA with oxazole-containing macrocyclic compounds Biochimie 2008, 90, 1233-1249.
28. Tsai, Y.C.; Qi, H.; Lin, C.P.; Lin, R.K.; Kerrigan, J.E.; Rzuczek S.G.; LaVoie, E.J.; Rice, J.E.; Pilch, D.S.; Lyu, Y.L.; et al. A G-quadruplex Stabilizer Induces M-phase Cell Cycle Arrest. J. Biol. Chem. 2009, 284, 22535-22543.
29. Rzuczek, S.G.; Pilch, D.S.; Liu, A.; Liu, L.; LaVoie, E.J.; Rice, J.E. Macrocyclic Pyridyl Polyoxazoles: Selective RNA and DNA G-Quadruplex Ligands as Antitumor Agents. J. Med. Chem. 2010. 53. 3632-3644.
30. Satyanarayana, M.; Kim, Y.A.; Rzuczek, S.G.; Pilch, D.S.; Liu, A.A.; Liu, L.F.; Rice, J.E.; LaVoie, E.J. Macrocyclic hexaoxazoles: Influence of aminoalkyl substituents on RNA and DNA G-quadruplex stabilization and cytotoxicity Bioorg. Med. Chem. Lett. 2010, 20, 3150-3154.
31. Tera, M.; Sohtome, Y.; Ishizuka H.; Doi, T.; Takagi, M.; Shin-ya, K.; Nagasawa, K. Design and synthesis of telomestatin derivatives and their inhibitory activity of telomerase. Heterocycles 2006, 69, 505-514.
32. Tera, M.; Ishizuka, H.; Takagi, M.; Suganuma, M.; Shin-ya, K.; Nagasawa, K. Macrocyclic Hexaoxazoles as Sequence- and Mode-Selective G-Quadruplex Binders. Angew. Chem. Int. Ed. 2008, 47, 5557-5560.
33. Majima, S.; Tera, M.; Iida, K.; Shin-ya, K.; Nagasawa, K. Design and synthesis of telomestatin derivatives containing Methyl Oxazole and their G-Quadruplex stabilizing activities. Heterocycles 2011, 82, 1345-1357.
34. Iida, K.; Majima, S.; Ohtake, T.; Tera, M.; Shin-ya, K.; Nagasawa, K. Design and synthesis of G-Quadruplex ligands bearing macrocyclic hexaoxazoles with four-way side chains. Heterocycles 2012, 84, 401-411.
35. Nakamura, T.; Iida, K.; Tera, M.; Shin-ya, K.; Seimiya, H.; Nagasawa, K. A Caged Ligand for a Telomeric G-Quadruplex. ChemBioChem 2012, 13, 774-777.
36. Iida, K.; Tera, M.; Hirokawa, T.; Shin-ya, K.; Nagasawa, K. G-quadruplex recognition by macrocyclic hexaoxazole (6OTD) dimer: greater selectivity than monomer. Chem. Commun. 2009, 6481-6483.
37. Iida, K.; Tera, M.; Hirokawa, T.; Shin-ya, K.; Nagasawa, K. Synthesis of Macrocyclic Hexaoxazole (6OTD) Dimers, Containing Guanidine and Amine Functionalized Side Chains, and an Evaluation of Their Telomeric G4 Stabilizing Properties. J. Nucleic Acids 2010, 2010, 217627.
38. Amemiya, Y.; Furunaga, Y.; Iida, K.; Tera, M.; Nagasawa, K.; Ikebukuro, K.; Nakamura, C. Analysis of the unbinding force between telomestatin derivatives and human telomeric G-quadruplex by atomic force microscopy Chem. Commun. 2011, 47, 7485-7487.
39. Tera, M.; Iida, K.; Ishizuka, H.; Takagi, M.; Suganuma, M.; Doi, T.; Shin-ya, K.; Nagasawa, K. Synthesis of a Potent G-Quadruplex-Binding Macrocyclic Heptaoxazole ChemBioChem 2009, 10, 431-435.
40. Tera, M.; Iida, K.; Ikebukuro, K.; Seimiya, H.; Shin-ya, K.; Nagasawa, K. Visualization of G-quadruplexes by using a BODIPY-labeled macrocyclic heptaoxazole. Org. Biomol. Chem. 2010, 8, 2749-2755.
41. We named the core structure of macrocyclic hexaoxazole of 2 as 6OTD (6 Oxazoles Telomestatin Derivative).
42. Xu, Y.; Ishizuka, T.; Kurabayashi, K.; Komiyama, M. Consecutive formation of G-quadruplexes in human telomeric-overhang DNA: A protective capping structure for telomere ends. Angew. Chem. Int. Ed. 2009, 48, 7833-7836.
43. Petraccone, L.; Trent, J.O.; Chaires, J.B. The tail of the telomere. J. Am. Chem. Soc. 2008, 130, 16530-16532.
44. Renciuk, D.; Kejnovska, I.; Skolakova, P.; Bednarova, K.; Motlova, J.; Vorlickova M. Arrangements of human telomere DNA quadruplex in physiologically relevant K+ solutions. Nucleic Acids Res. 2009, 37, 6625-6634.
45. Vorlickova, M.; Chladkova, J.; Kejnovska, I., Fialova, M.; Kypr J. Guanine tetraplex topology of human telomere DNA is governed by the number of (TTAGGG) repeats. Nucleic Acids Res. 2005, 33, 5851-5860.
46. Singh, V.; Azarkh, M.; Drescher, M.; Hartig, J. S. Conformations of individual quadruplex units studied in the context of extended human telomeric DNA. Chem. Commun. 2012, 48, 8258-8260.
47. Petraccone, L.; Spink, C.; Trent, J.O.; Garbett, N.C.; Mekmaysy, C.S.; Giancola, C., Chaires, J.B. Structure and stability of higher-order human telomeric quadruplexes. J. Am. Chem. Soc. 2011, 133, 20951-20961.
48. Yu, H.Q.; Miyoshi, D.; Sugimoto, N. Characterization of structure and stability of long telomeric DNA G-quadruplexes. J. Am. Chem. Soc. 2006, 128, 15461-15468.
49. Yu, H.; Gu, X.; Nakano, S.; Miyoshi, D.; Sugimoto, N. Beads-on-a-string structure of long telomeric DNAs under molecular crowding conditions. J. Am. Chem. Soc. 2012, 134, 20060-20069.
50. Haider, S.; Parkinson, G.N.; Neidle, S. Molecular dynamics and principal components analysis of human telomeric quadruplex multimers. Biophys. J. 2008, 95, 296-311.
51. Haider, S.; Neidle, S. A molecular model for drug binding to tandem repeats of telomeric G-quadruplexes. Biochem. Soc. Trans. 2009, 37, 583-588.
52. Chang, C.C.; Chien, C.W.; Lin, Y.H.; Kang, C.C.; Chang T.C. Investigation of spectral conversion of d(TTAGGG)4 and d(TTAGGG)13 upon potassium titration by a G-quadruplex recognizer BMVC molecule. Nucleic Acids Res. 2007, 35, 2846-2860.
53. Iida, K.; Tsubouchi, G.; Nakamura, T.; Majima, S.; Seimiya, H.; Nagasawa, K. Interaction of long telomeric DNAs with macrocyclic hexaoxazole as a G-quadruplex ligand. Med. Chem. Commun. 2013, 4, 260-264.
54. The dimer 3 was found to form a complex with telo24 in 1:1 ratio based upon the electrospray ionization mass spectra (see Supplementary Information).
55. We prepared long telomeric DNAs consisting of 48, 72, and 96 bases, i.e., (TTAGGG)n (n = 8, 12, 16; telo48, telo72, and telo96, corresponding to two, three and four units of telo24, respectively). The DNAs were purchased from Sigma Genosys. See table below for sequences of telomeric DNAs used in this work.
56. Balagurumoorthy, P., Brahmachari, S.K. Structure and stability of human telomeric sequence. J. Biol. Chem. 1994, 269, 21858-21869.
57. TRAP lysis buffer was prepared as follows; 400 μL of 1 M Tris-HCl (pH 8.0), 40 μL of 1 M MgCl2 aq, 200 μL of 0.2 M EGTA, 2 mL of 10% CHAPS, 8 mL of 50% glycerol and 25 mL of RNase free H2O were mixed. Next, HCl aq was added to the mixture (final; pH 7.5), which was diluted to 40 mL with MilliQ water and filtered. Then, 1.0 μL of 0.1 M 4-(2- aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) and 0.35 μL of 2-mercaptoethanol were added to 1.0 mL of the mixture.