Nucleic Acids Research, 2001, Vol. 29, No. 5 1087-1096
© 2001 Oxford University Press
Ethidium derivatives bind to G-quartets, inhibit telomerase and act as fluorescent probes for quadruplexes
Laboratoire de Biophysique, Muséum National d’Histoire Naturelle, INSERM U201, CNRS UMR 8646, 43 rue Cuvier, 75005 Paris, France and 1Centre de Recherche de Vitry-Alfortville, Aventis-Pharma S.A., 94400 Vitry-sur-Seine Cedex, France
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 describe ethidium derivatives that stabilize G-quadruplexes. These molecules were shown to increase the melting temperature of an intramolecular quadruplex structure, as shown by fluorescence and absorbance measurements, and to facilitate the formation of intermolecular quadruplex structures. In addition, these molecules may be used to reveal the formation of multi-stranded DNA structures by standard fluorescence imaging, and therefore become fluorescent probes of quadruplex structures. This recognition was associated with telomerase inhibition in vitro: these derivatives showed a potent anti-telomerase activity, with IC50 values of 18–100 nM in a standard TRAP assay.
* To whom correspondence should be addressed. Tel: +33 1 40 79 36 89; Fax: +33 1 40 79 37 05; Email: mergny{at}vnumail.com Present addresses Paola B. Arimondo, UMR 176 CNRS, Institut Curie, Section Recherche, 26 rue d’Ulm, 75005 Paris, France Jean-Francois Riou, Unité MéDIAN CNRS FRE 2141, UFR de pharmacie Université de Reims, France
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. N. Lane, J. B. Chaires, R. D. Gray, and J. O. Trent Stability and kinetics of G-quadruplex structures Nucleic Acids Res., August 21, 2008; (2008) gkn517v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Brassart, D. Gomez, A. D. Cian, R. Paterski, A. Montagnac, K.-H. Qui, N. Temime-Smaali, C. Trentesaux, J.-L. Mergny, F. Gueritte, et al. A New Steroid Derivative Stabilizes G-Quadruplexes and Induces Telomere Uncapping in Human Tumor Cells Mol. Pharmacol., September 1, 2007; 72(3): 631 - 640. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Barbieri, A. R. Srinivasan, S. G. Rzuczek, J. E. Rice, E. J. LaVoie, and D. S. Pilch Defining the mode, energetics and specificity with which a macrocyclic hexaoxazole binds to human telomeric G-quadruplex DNA Nucleic Acids Res., May 11, 2007; 35(10): 3272 - 3286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Cian and J.-L. Mergny Quadruplex ligands may act as molecular chaperones for tetramolecular quadruplex formation Nucleic Acids Res., April 3, 2007; 35(8): 2483 - 2493. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Gomez, T. Wenner, B. Brassart, C. Douarre, M.-F. O'Donohue, V. El Khoury, K. Shin-ya, H. Morjani, C. Trentesaux, and J.-F. Riou Telomestatin-induced Telomere Uncapping Is Modulated by POT1 through G-overhang Extension in HT1080 Human Tumor Cells J. Biol. Chem., December 15, 2006; 281(50): 38721 - 38729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. He, R. D. Neumann, and I. G. Panyutin Intramolecular quadruplex conformation of human telomeric DNA assessed with 125I-radioprobing Nucleic Acids Res., October 8, 2004; 32(18): 5359 - 5367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Biroccio and C. Leonetti Telomerase as a new target for the treatment of hormone-refractory prostate cancer Endocr. Relat. Cancer, September 1, 2004; 11(3): 407 - 421. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. C. Hahn Role of Telomeres and Telomerase in the Pathogenesis of Human Cancer J. Clin. Oncol., May 15, 2003; 21(10): 2034 - 2043. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Thorpe, S. C. M. Teixeira, B. C. Gale, and C. J. Cardin Crystal structure of the complementary quadruplex formed by d(GCATGCT) at atomic resolution Nucleic Acids Res., February 1, 2003; 31(3): 844 - 849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Gowan, J. R. Harrison, L. Patterson, M. Valenti, M. A. Read, S. Neidle, and L. R. Kelland A G-Quadruplex-Interactive Potent Small-Molecule Inhibitor of Telomerase Exhibiting in Vitro and in Vivo Antitumor Activity Mol. Pharmacol., May 1, 2002; 61(5): 1154 - 1162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-L. Mergny, J.-F. Riou, P. Mailliet, M.-P. Teulade-Fichou, and E. Gilson Natural and pharmacological regulation of telomerase Nucleic Acids Res., February 15, 2002; 30(4): 839 - 865. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Riou, L. Guittat, P. Mailliet, A. Laoui, E. Renou, O. Petitgenet, F. Megnin-Chanet, C. Helene, and J. L. Mergny Cell senescence and telomere shortening induced by a new series of specific G-quadruplex DNA ligands PNAS, February 14, 2002; (2002) 52698099. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Duan, A. Rangan, H. Vankayalapati, M.-Y. Kim, Q. Zeng, D. Sun, H. Han, O. Yu. Fedoroff, D. Nishioka, S. Y. Rha, et al. Design and Synthesis of Fluoroquinophenoxazines That Interact with Human Telomeric G-Quadruplexes and Their Biological Effects Mol. Cancer Ther., December 1, 2001; 1(2): 103 - 120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Gowan, R. Heald, M. F. G. Stevens, and L. R. Kelland Potent Inhibition of Telomerase by Small-Molecule Pentacyclic Acridines Capable of Interacting with G-Quadruplexes Mol. Pharmacol., November 1, 2001; 60(5): 981 - 988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-L. Mergny, L. Lacroix, M.-P. Teulade-Fichou, C. Hounsou, L. Guittat, M. Hoarau, P. B. Arimondo, J.-P. Vigneron, J.-M. Lehn, J.-F. Riou, et al. Telomerase inhibitors based on quadruplex ligands selected by a fluorescence assay PNAS, March 13, 2001; 98(6): 3062 - 3067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Riou, L. Guittat, P. Mailliet, A. Laoui, E. Renou, O. Petitgenet, F. Megnin-Chanet, C. Helene, and J. L. Mergny Cell senescence and telomere shortening induced by a new series of specific G-quadruplex DNA ligands PNAS, March 5, 2002; 99(5): 2672 - 2677. [Abstract] [Full Text] [PDF]
|
|