| | |  | | | | Record from Web of Science® | | | | | | |
| Quadruplex ligands may act as molecular chaperones for tetramolecular quadruplex formation |
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| Author(s): De Cian A (De Cian, Anne), Mergny JL (Mergny, Jean-Louis) |
| Source: NUCLEIC ACIDS RESEARCH Volume: 35 Issue: 8 Pages: 2483-2493 Published: APR 2007 |
| Times Cited: 18 References: 65 |
| Abstract: 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, k(off)) or whether ligands actively promote the formation of the complex and act as quadruplex chaperones by increasing the association constant, k(on). 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Mergny, JL (reprint author), CNRS, INSERM, UR 565, USM 503,Museum Natl Hist Nat,Lab Biophys,UMR 5153, 43 Rue Cuvier, F-75231 Paris 05, France |
Addresses:
1. CNRS, INSERM, UR 565, USM 503,Museum Natl Hist Nat,Lab Biophys,UMR 5153, F-75231 Paris 05, France |
| Publisher: OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: 178SE |
| ISSN: 0305-1048 |
| DOI: 10.1093/nar/gkm098 |
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