期刊
NUCLEIC ACIDS RESEARCH
卷 39, 期 4, 页码 -出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkq1199
关键词
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资金
- INSERM
- ARC
- CNRS-MNHN
- Fondation pour la Recherche Medicale, Region Aquitaine
- CNRS-PIR
- INSERM [U565]
- CNRS-MNHN [UMR7196]
- Museum National d'Histoire Naturelle, 43 rue Cuvier, 75005 Paris, France
- [ANR-09-Blanc-0355]
RNA and DNA guanine-rich sequences can adopt unusual structures called Guanine quadruplexes (G4). A quadruplex-prone RNA sequence is present at the 5'-end of the 451-nt-long RNA component of telomerase, hTERC. As this quadruplex may interfere with P1 helix formation, a key structural element for this RNA, we are seeking molecules that would alter this RNA duplex-quadruplex equilibrium. In this work, we present a fluorescence-based test designed to identify G4 ligands specific for the hTERC G-rich motif and that can prevent P1 helix formation. From an initial panel of 169 different molecules, 11 were found to be excellent P1 duplex inhibitors. Interestingly, some of the compounds not only exhibit a strong selectivity for quadruplexes over duplexes, but also demonstrated a preference for G4-RNA over all other quadruplexes. This test may easily be adapted to almost any quadruplex-forming sequence and converted into HTS format.
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