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  • Title: Selective and Cooperative Ligand Binding to Antiparallel Human Telomeric DNA G-Quadruplexes.
    Author: Marchand A, Strzelecka D, Gabelica V.
    Journal: Chemistry; 2016 Jul 04; 22(28):9551-5. PubMed ID: 27168452.
    Abstract:
    The quest for ligands that specifically bind 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. 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 into an antiparallel three-quartet topology upon binding of two ligands.
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