title: Human telomeric G-quadruplex DNA interactions of N-phenanthroline glycosylamine copper(II) complexes.
abstract: We report in this article the interactions of five N-(1,10-phenanthrolin-5-yl)-β-glycopyranosylamine copper(II) complexes with G-quadruplex DNA. Specifically, the interactions of these compounds with a human telomeric oligonucleotide have been assessed by fluorescence-based assays (FRET melting and G4-FID), circular dichroism and competitive equilibrium dialysis experiments. The metal complexes bind and stabilize G-quadruplex DNA structures with apparent association constants in the order of 10(4)-10(5)M(-1) and the affinity observed is dependent on the ionic conditions utilized and the specific nature of the carbohydrate moiety tethered to the 1,10-phenanthroline system. The compounds showed only a slight preference to bind G-quadruplex DNA over duplex DNA when the quadruplex DNA was folded in sodium ionic conditions. However, the binding affinity and selectivity, although modest, were notably increased when the G-quadruplex DNA was folded in the presence of potassium metal ions. Moreover, the study points towards a significant contribution of groove and/or loop binding in the recognition mode of quadruplex structures by these non-classical quadruplex ligands. The results reported herein highlight the potential and the versatility of carbohydrate bis-phenanthroline metal-complex conjugates to recognize G-quadruplex DNA structures.
authors.affiliation: Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28805 Alcalá de Henares (Madrid), Spain.
authors.forename: Katerina
authors.initials: K
authors.lastname: Duskova
authors.affiliation: Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28805 Alcalá de Henares (Madrid), Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Sierra
authors.affiliation: Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28805 Alcalá de Henares (Madrid), Spain.
authors.forename: María-Selma
authors.initials: MS
authors.lastname: Arias-Pérez
authors.affiliation: Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28805 Alcalá de Henares (Madrid), Spain. Electronic address: lourdes.gude@uah.es.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Gude
mesh_terms: D000606:Amino Sugars / Q000138:chemical synthesis / Q000737:chemistry*; D002942:Circular Dichroism; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D006801:Humans; D008024:Ligands; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010618:Phenanthrolines / Q000138:chemical synthesis / Q000737:chemistry*; D011189:Potassium Chloride / Q000737:chemistry; D012965:Sodium Chloride / Q000737:chemistry; D016615:Telomere / Q000737:chemistry
chemical_list: D000606:Amino Sugars; D056831:Coordination Complexes; D008024:Ligands; D009838:Oligodeoxyribonucleotides; D010618:Phenanthrolines; D012965:Sodium Chloride; D011189:Potassium Chloride; D003300:Copper
keywords: 1,10-Phenanthroline; Copper(II) complexes; DNA interactions; G-quadruplex DNA; Glycosylamines