Journal
CHEMISTRY-A EUROPEAN JOURNAL
Volume 22, Issue 28, Pages 9551-9555Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201601937
Keywords
affinity; cooperativity; G-quadruplexes; ligands; mass spectrometry
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Funding
- Inserm (ATIP-Avenir Grant) [R12086GS]
- Conseil Regional Aquitaine [20121304005]
- EU [FP7-PEOPLE-2012-CIG-333611, ERC-2013-CoG-616551]
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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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