title: Selective and Cooperative Ligand Binding to Antiparallel Human Telomeric DNA G-Quadruplexes.
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.
authors.affiliation: Université de Bordeaux, IECB, ARNA Laboratory, 33600, Pessac, France.|Inserm, U1212, ARNA Laboratory, 33000, Bordeaux, France.|CNRS, UMR 5320, ARNA Laboratory, 33400, Talence, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Marchand
authors.affiliation: Université de Bordeaux, IECB, ARNA Laboratory, 33600, Pessac, France.|Inserm, U1212, ARNA Laboratory, 33000, Bordeaux, France.|Division of Biophysics, Institute of Experimental Physics, University of Warsaw, Warsaw, Poland.
authors.forename: Dominika
authors.initials: D
authors.lastname: Strzelecka
authors.affiliation: Université de Bordeaux, IECB, ARNA Laboratory, 33600, Pessac, France. valerie.gabelica@inserm.fr.|Inserm, U1212, ARNA Laboratory, 33000, Bordeaux, France. valerie.gabelica@inserm.fr.|CNRS, UMR 5320, ARNA Laboratory, 33400, Talence, France. valerie.gabelica@inserm.fr.
authors.forename: Valerie
authors.identifier: http://orcid.org/0000-0001-9496-0165
authors.initials: V
authors.lastname: Gabelica
mesh_terms: D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D021241:Spectrometry, Mass, Electrospray Ionization; D016615:Telomere / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008024:Ligands; D004247:DNA
keywords: G-quadruplexes; affinity; cooperativity; ligands; mass spectrometry