Nucleic Acids Research Advance Access originally published online on March 29, 2007
Nucleic Acids Research 2007 35(8):2483-2493; doi:10.1093/nar/gkm098
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Nucleic Acids Research, 2007, Vol. 35, No. 8 2483-2493
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Structural Biology |
Quadruplex ligands may act as molecular chaperones for tetramolecular quadruplex formation
Laboratoire de Biophysique, Muséum National d'Histoire Naturelle USM 503, INSERM UR 565, CNRS UMR 5153, 43 rue Cuvier, 75231 Paris cedex 05, France
*To whom correspondence should be addressed. Tel: +33 1 40 79 36 89; Fax: +33 1 40 79 37 05; Email: mergny{at}mnhn.fr
Received December 22, 2006. Revised February 3, 2007. Accepted February 3, 2007.
G-quadruplexes are a family of four-stranded DNA structures, stabilized by G-quartets, that form in the presence of monovalent cations. Efforts are currently being made to identify ligands that selectively bind to G-quadruplex motifs as these compounds may interfere with the telomere structure, telomere elongation/replication and proliferation of cancer cells. The kinetics of quadruplex–ligands interactions are poorly understood: it is not clear whether quadruplex ligands lock into the preformed structure (i.e. increase the lifetime of the structure by lowering the dissociation constant, koff) or whether ligands actively promote the formation of the complex and act as quadruplex chaperones by increasing the association constant, kon. We studied the effect of a selective quadruplex ligand, a bisquinolinium pyridine dicarboxamide compound called 360A, to distinguish these two possibilities. We demonstrated that, in addition to binding to and locking into preformed quadruplexes, this molecule acted as a chaperone for tetramolecular complexes by acting on kon. This observation has implications for in vitro and in vivo applications of quadruplexes and should be taken into account when evaluating the cellular responses to these agents.
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