title: Molecular Basis for Differential Recognition of G-Quadruplex versus Double-Helix DNA by Bis-Phenanthroline Metal Complexes.
abstract: 1,10-Phenanthroline (Phen) derivatives are attractive ligands to provide metal complexes that are selective for different DNA secondary structures. Herein, we analyze the binding processes of two bis-Phen analogues and their Ni(II) complexes toward double-stranded DNA and telomeric G-quadruplex DNA by calorimetric and spectroscopic techniques. The free ligands can adapt to both DNA arrangements. Conversely, metal ion coordination produces an increase in ligand affinity for the tetrahelical structure, whereas it dramatically decreases binding to double-stranded DNA as a result of distinct binding modes on the two templates. In fact, Ni(II) complexes effectively stack on the G-quadruplex terminals, with an entropic loss counterbalanced by favorable enthalpy changes, whereas they cause a conformational reshaping of the double-helix form with a substantial decrease in the binding free energy. Consistently, no Ni(II) -DNA ionic pair has ever been identified. These results provide a rationale for the selective recognition of distinct DNA arrangements in view of targeted pharmacological applications.
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, v. Marzolo 5, 35131, Padova, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Rigo
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, v. Marzolo 5, 35131, Padova, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Bianco
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, v. Marzolo 5, 35131, Padova, Italy.|GlaxoSmithKline, 1250 S. Collegeville Road, Collegeville, PA, 19426, USA.
authors.forename: Caterina
authors.initials: C
authors.lastname: Musetti
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, v. Marzolo 5, 35131, Padova, Italy.
authors.forename: Manlio
authors.initials: M
authors.lastname: Palumbo
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, v. Marzolo 5, 35131, Padova, Italy. claudia.sissi@unipd.it.
authors.forename: Claudia
authors.identifier: 0000-0002-9713-1415
authors.initials: C
authors.lastname: Sissi
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D054856:G-Quadruplexes / Q000187:drug effects*; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D009532:Nickel / Q000737:chemistry / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010618:Phenanthrolines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D008024:Ligands; D009942:Organometallic Compounds; D010618:Phenanthrolines; D009532:Nickel; D004247:DNA
keywords: DNA recognition; G-quadruplexes; helical structures; nickel; phenanthroline ligands