title: Thermodynamic fingerprints of ligand binding to human telomeric G-quadruplexes.
abstract: Thermodynamic studies of ligand binding to human telomere (ht) DNA quadruplexes, as a rule, neglect the involvement of various ht-DNA conformations in the binding process. Therefore, the thermodynamic driving forces and the mechanisms of ht-DNA G-quadruplex-ligand recognition remain poorly understood. In this work we characterize thermodynamically and structurally binding of netropsin (Net), dibenzotetraaza[14]annulene derivatives (DP77, DP78), cationic porphyrin (TMPyP4) and two bisquinolinium ligands (Phen-DC3, 360A-Br) to the ht-DNA fragment (Tel22) AGGG(TTAGGG)3 using isothermal titration calorimetry, CD and fluorescence spectroscopy, gel electrophoresis and molecular modeling. By global thermodynamic analysis of experimental data we show that the driving forces characterized by contributions of specific interactions, changes in solvation and conformation differ significantly for binding of ligands with low quadruplex selectivity over duplexes (Net, DP77, DP78, TMPyP4; KTel22 ≈ <KdsDNA) and for highly selective quadruplex-specific ligands (Phen-DC3, 360A-Br; KTel22 > KdsDNA). These contributions are in accordance with the observed structural features (changes) and suggest that upon binding Net, DP77, DP78 and TMPyP4 select hybrid-1 and/or hybrid-2 conformation while Phen-DC3 and 360A-Br induce the transition of hybrid-1 and hybrid-2 to the structure with characteristics of antiparallel or hybrid-3 type conformation.
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia.
authors.forename: Matjaž
authors.initials: M
authors.lastname: Bončina
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia.
authors.forename: Črtomir
authors.initials: Č
authors.lastname: Podlipnik
authors.affiliation: Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, PO Box 180, HR-10002 Zagreb, Croatia.
authors.forename: Ivo
authors.identifier: http://orcid.org/0000-0002-9933-446X
authors.initials: I
authors.lastname: Piantanida
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Kraków, Poland.
authors.forename: Julita
authors.initials: J
authors.lastname: Eilmes
authors.affiliation: Institut Curie, CNRS UMR-176, Centre Universitaire d'Orsay, Paris-Sud 91405 Orsay Cedex, France.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Teulade-Fichou
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia.
authors.forename: Gorazd
authors.initials: G
authors.lastname: Vesnaver
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia jurij.lah@fkkt.uni-lj.si.
authors.forename: Jurij
authors.initials: J
authors.lastname: Lah
mesh_terms: D004247:DNA / Q000737:chemistry; D054856:G-Quadruplexes; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D016615:Telomere / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D008024:Ligands; D004247:DNA