An Acyclic Oligoheteroaryle That Discriminates Strongly between Diverse G-Quadruplex Topologies


  • We gratefully acknowledge D. Grierson for fruitful discussion, Marianne Blombled for LC-MS analysis, the MENRT for a PhD fellowship to M.R.D., the CNRS and the Institut Curie for a joint PhD fellowship to E.L., the LNCC for a grant (Equipe Labellisée) to J.F.R. and a PhD fellowship to A.S., and the ANR for financial support to F.H. (ANR-09-BLAN-0355 “G4Toolbox”). Nicolas Saettel is especially acknowledged for his help in the docking experiment.


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Feeling groovy: A family of nonmacrocyclic G-quadruplex binders with alternate oxazole and pyridine motifs was prepared. The shown heptacyclic derivative exhibits an unprecedented binding preference for certain quadruplex topologies: it recognizes exclusively the human telomeric quadruplex in Na+ buffer but not in K+ buffer. This unique quadruplex binding profile is strongly dependent on the size of the ligand and may result from groove interactions.