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Selective and Cooperative Ligand Binding to Antiparallel Human Telomeric DNA G‐Quadruplexes
Author(s) -
Marchand Adrien,
Strzelecka Dominika,
Gabelica Valerie
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201601937
Subject(s) - antiparallel (mathematics) , g quadruplex , circular dichroism , chemistry , telomere , cooperativity , nucleic acid , affinities , stereochemistry , dna , crystallography , molecule , ligand (biochemistry) , biophysics , biology , biochemistry , receptor , physics , organic chemistry , quantum mechanics , magnetic field
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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