mass spectrometry; DNA; nonconvalent; quadruplex; triplex; G-quadruplex
Abstract :
[en] The telomeric G-rich single-stranded DNA can adopt in vitro an intramolecular quadruplex structure, which has been shown to directly inhibit telomerase activity. The reactivation of this enzyme in immortalized and most cancer cells suggests that telomerase is a relevant target in oncology, and telomerase inhibitors have been proposed as new potential anticancer agents. In this paper, we have analyzed the selectivity of four ethidium derivatives and ethidium itself toward different G-quadruplex species, with electrospray mass spectrometry and competitive equilibrium dialysis and evaluated their inhibitory properties against telomerase. A selectivity profile may be obtained through electrospray ionization mass spectrometry (ESI-MS), which is in fair agreement with competitive equilibrium dialysis data. It also provides unambiguous data on the number of binding sites per nucleic acid (maximal number of two ethidium derivatives per quadruplex, in agreement with external stacking). Our experiments also demonstrate that one compound (4) is the most active and selective G-quadruplex ligand within this series and the most selective telomerase inhibitor in a modified TRAP-G4 assay.
Research Center/Unit :
Giga-Systems Biology and Chemical Biology - ULiège CART - Centre Interfacultaire d'Analyse des Résidus en Traces - ULiège
Griffith, J. D., Comeau, L., Rosenfield, S., Stansel, R. M., Bianchi, A., Moss, H., and de Lange, T. (1999) Cell 97, 503-514.
Voloshin, O. N., Veselkov, A. G., Belotserkovskii, B. P., Danilevskaya, O. N., Pavlova, M. N., Dobrynin, V. N., and Frank-Kamenetskii, M. D. (1992) J. Biomol. Struct. Dyn. 9, 643-652.
Wang, Y., and Patel, D. J. (1993) Structure 1, 263-282.
Parkinson, G. N., Lee, M. P. H., and Neidle, S. (2002) Nature 417, 876-880.
Schaffitzel, C., Berger, I., Postberg, J., Hanes, J., Lipps, H. J., and Plückthun, A. (2001) Proc. Natl. Acad. Sci. U.S.A. 98, 8572-8577.
Siddiqui-Jain, A., Grand, C. L., Bearss, D. J., and Hurley, L. H. (2002) Proc. Natl. Acad. Sci. U.S.A. 99, 11593-11598.
Hurley, L. H. (2002) Nat. Rev. Cancer 2, 188-200.
Zahler, A. M., Williamson, J. R., Cech, T. R., and Prescott, D. M. (1991) Nature 350, 718-720.
Sun, D., Thompson, B., Cathers, B. E., Salazar, M., Kerwin, S. M., Trent, J. O., Jenkins, T. C., Neidle, S., and Hurley, L. H. (1997) J. Med. Chem. 40, 2113-2116.
Mergny, J. L., and Hélène, C. (1998) Nature Med. 4, 1366-1367.
Oka, Y., and Thomas, C. A., Jr. (1987) Nucleic Acids Res. 15, 8877-8898.
Sen, D., and Gilbert, W. (1988) Nature 334, 364-366.
Sen, D., and Gilbert, W. (1990) Nature 344, 410-414.
Sundquist, W. I., and Klug, A. (1989) Nature 342, 825-829.
Williamson, J. R. (1994) Annu. Rev. Biophys. Biomol. Struct. 23, 703-730.
Anantha, N. V., Azam, M., and Sheardy, R. D. (1998) Biochemistry 37, 2709-2714.
Arthanari, H., Basu, S., Kawano, T. L., and Bolton, P. H. (1998) Nucleic Acids Res. 26, 3724-3728.
Han, F. X. G., Wheelhouse, R. T., and Hurley, L. H. (1999) J. Am. Chem. Soc. 121, 3561-3570.
Fedoroff, O. Y., Salazar, M., Han, H., Chemeris, V. V., Kerwin, S. M., and Hurley, L. H. (1998) Biochemistry 37, 12367-12374.
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., and Neidle, S. (1998) J. Med. Chem. 41, 4873-4884.
Perry, P. J., Read, M. A., Davies, R. T., Gowan, S. M., Reszka, A. P., Wood, A. A., Kelland, L. R., and Neidle, S. (1999) J. Med. Chem. 42, 2679-2684.
Read, M., Harrison, R. J., Romagnoli, B., Tanious, F. A., Gowan, S. H., Reszka, A. P., Wilson, W. D., Kelland, L. R., and Neidle, S. (2001) Proc. Natl. Acad. Sci. U.S.A. 98, 4844-4849.
Riou, J. F., Guittat, L., Renou, E., Mailliet, P., Laoui, A., Petigenet, O., Hélène, C., and Mergny, J. L. (2002) Proc. Natl. Acad. Sci. U.S.A. 99, 2672-2677.
Kim, M. Y., Vankayalapati, H., Shin-Ya, K., Wierzba, K., and Hurley, L. H. (2002) J. Am. Chem. Soc. 124, 2098-2099.
Caprio, V., Guyen, B., OpokuBoahen, Y., Mann, J., Gowan, S. M., Kelland, L. M., Read, M. A., and Neidle, S. (2000) Bioorg. Med. Chem. Lett. 10, 2063-2066.
Kerwin, S. M. (2000) Curr. Pharm. Des. 6, 441-471.
Cuesta, J., Read, M., and Neidle, S. (2003) Mini Rev. Med. Chem. 3, 11-21.
Le Pecq, J. B., and Paoletti, C, (1967) J, Mol. Biol. 27, 87-106.
Mergny, J. L., Collier, D., Rougée, M., Montenay-Garestier, T., and Hélène, C. (1991) Nucleic Acids Res. 19, 1521-1526.
Scaria, P. V., and Shafer, R. H. (1991) J. Biol. Chem. 266, 5417-5423.
Guo, Q., Lu, M., Marky, L. A., and Kallenbach, N. R. (1992) Biochemistry 31, 2451-2455.
Shida, T., Ikeda, N., and Sekiguchi, J. (1996) Nucleosides Nucleotides 15, 599-605.
Ren, J. S., and Chaires, J. B. (1999) Biochemistry 38, 16067-16075.
Koeppel, F., Riou, J. F., Laoui, A., Mailliet, P., Arimondo, P. B., Labit, D., Petigenet, O., Hélène, C., and Mergny, J. L. (2001) Nucleic Acids Res. 29, 1087-1096.
Cain, B. F., Atwell, G. J., and Seelye, R. N. (1969) J. Med. Chem. 12, 199-206.
Berg, S. S. (1960) Nature 188, 1106-1107.
Wragg, W. R., Washbourn, K., Brown, K. N., and Hill, J. (1958) Nature 182, 1005.
Alberti, P., Schmidt, P., Nguyen, C. H., Hoarau, M., Grierson, D., and Mergny, J. L. (2002) Bioorg. Med. Chem. Lett. 12, 1071-1074.
Alberti, P., Hoarau, M., Guittat, L., Takasugi, M., Arimondo, P. B., Lacroix, L., Mills, M., Teulade-Fichou, M. P., Vigneron, J. P., Lehn, J. M., Mailliet, P., and Mergny, J. L. (2002) in Small molecule DNA and RNA binders: from synthesis to nucleic acid complexes (Bailly, C., Demeunynck, M., and Wilson, D., Eds.) pp 315-336, Wiley VCH, New York.
Guittat, L., Alberti, P., Rosu, F., Van Miert, S., Thetiot, E., Pieters, L., Gabelica, V., De Pauw, E., Ottaviani, A., Riou, J. F., and Mergny, J.-L. (2003) Biochimie 85, 535-547.
Mills, M., Arimondo, P., Lacroix, L., Garestier, T., Hélè ne, C., Klump, H. H., and Mergny, J. L. (1999) J. Mol. Biol. 291, 1035-1054.
Phan, A. T., and Leroy, J. L. (2002) J. Biomol. Struct. Dyn. Spec. Issue S2, 245-252.
Ren, J. S., and Chaires, J. B. (2000) J. Am. Chem. Soc. 122, 424-425.
Ren, J. S., Bailly, C., and Chaires, J. B. (2000) FEBS Lett. 470, 355-359.
Ren, J., Qu, X., Dattagupta, N., and Chaires, J. B. (2001) J. Am. Chem. Soc. 123, 6742-6743.
Ren, J. S., and Chaires, J. B. (2001) in Drug Nucleic Acid Interaction (Chaires, J. B., and Waring, M. J., Eds.) pp 99-108, Academic Press Inc., San Diego, CA.
Alberti, P., Ren, J., Teulade-Fichou, M. P., Guittat, L., Riou, J. F., Chaires, J. B., Hélène, C., Vigneron, J. P., Lehn, J. M., and Mergny, J. L. (2001) J. Biomol. Struct. Dyn. 19, 505-513.
Rosu, F., Gabelica, V., Houssier, C., Colson, P., and De Pauw, E. (2002) Rapid Commun. Mass Spectrom. 16, 1729-1736.
Rosu, F., Gabelica, V., Houssier, C., and DePauw, E. (2002) Nucleic Acids Res. 30, e82.
Mergny, J. L. (1999) Biochemistry 38, 1573-1581.
Mergny, J. L., and Maurizot, J. C. (2001) ChemBioChem 2, 124-132.
Fu, W. M., Begley, J. G., Killen, M. W., and Mattson, M. P. (1999) J. Biol. Chem. 274, 7264-7271.
Gomez, D., Mergny, J. L., and Riou, J. F. (2002) Cancer Res. 62, 3365-3368.
Hofstadler, S. A., and Griffey, R. H. (2001) Chem. Rev. 101, 377-390.
Beck, J., Colgrave, M. L., Ralph, S. F., and Sheil, M. M. (2001) Mass Spectrom. Rev. 20, 61-87.
Gabelica, V., DePauw, E., and Rosu, F. (1999) J. Mass Spectrometry 34, 1328-1337.
Wan, K. X., Shibue, T., and Gross, M. L. (2000) J. Am. Chem. Soc. 122, 300-307.
Carrasco, C., Rosu, F., Gabelica, V., Houssier, C., De Pauw, E., Garbay-Jaureguiberry, C., Roques, B., Wilson, W. D., Chaires, J. B., Waring, M. J., and Bailly, C. (2002) ChemBioChem 3, 100-106.
Mergny, J. L., Lacroix, L., Teulade-Fichou, M. P., Hounsou, C., Guittat, L., Hoarau, M., Arimondo, P. B., Vigneron, J. P., Lehn, J. M., Riou, J. F., Garestier, T., and Hélène, C. (2001) Proc. Natl. Acad. Sci. U.S.A. 98, 3062-3067.
Darby, R., Sollogoub, M., McKeen, C., Brown, L., Risitano, A., Brown, N., Barton, C., Brown, T., and Fox, K. (2002) Nucleic Acids Res. 30, e39.
Chen, Q., Kuntz, I. D., and Shafer, R. H. (1996) Proc. Natl. Acad. Sci. U.S.A. 93, 2635-2639.
Shafer, R. H. (1998) in Progress in Nucleic Acid Research (Moldave, K., Ed.) pp 55-94, Academic Press Inc., New York.
Han, H. Y., Hurley, L. H., and Salazar, M. (1999) Nucleic Acids Res. 27, 537-542.
Perry, P. J., and Jenkins, T. C. (2001) Mini Rev. Med. Chem. 1, 31-41.
Read, M., and Neidle, S. (2000) Biochemistry 39, 13422-13432.
Clark, G. R., Pytel, P. D., Squire, C. J., and Neidle, S. (2003) J. Am. Chem. Soc. 125, 4066-4067.
