Selective and Cooperative Ligand Binding to Antiparallel Human Telomeric DNA G-Quadruplexes

Abstract : The quest for ligands that bind specifically to particular G-quadruplex nucleic acid structures is particularly important to conceive molecules with specific effects on gene expression or telomere maintenance, or conceive structure-specific molecular probes. Here, using electrospray mass spectrometry in native conditions, we reveal a highly cooperative and selective 2:1 binding of Cu(II)-tolylterpyridine complexes to human telomeric G-quadruplexes. Circular dichroism and comparisons of affinities for different sequences reveal a marked preference for antiparallel structures with diagonal loops and/or wide-medium-narrow-medium groove width order. The cooperativity is attributed to conformational changes in the polymorphic telomeric G-quadruplex sequences, which convert preferably to an antiparallel, 3-quartet topology upon binding two ligands.
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Adrien Marchand, Dominika Strzelecka, Valérie Gabelica. Selective and Cooperative Ligand Binding to Antiparallel Human Telomeric DNA G-Quadruplexes. Chemistry - A European Journal, Wiley-VCH Verlag, 2016, 22 (28), pp.9551-9555. ⟨http://onlinelibrary.wiley.com/doi/10.1002/chem.201601937/full⟩. ⟨10.1002/chem.201601937⟩. ⟨hal-01537094⟩

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