title: The nickel(II) complex of guanidinium phenyl porphyrin, a specific G-quadruplex ligand, targets telomeres and leads to POT1 mislocalization in culture cells.
abstract: With the aim of finding selective and biologically active G-quadruplex ligands, modified porphyrin with bulky cationic substituents, meso-5,10,15,20-tetrakis(4-guanidinophenyl)porphyrin tetrahydrochloride, referred to as guanidinium phenyl porphyrin, was prepared. The corresponding nickel(II) and cobalt(III) metallated porphyrins were also synthesized. Interaction with quadruplexes was examined by means of fluorescence resonance energy transfer melting and surface plasmon resonance-based assays: the three compounds proved to bind to G-quadruplex DNA in a similar and highly selective way. Guanidinium phenyl porphyrin and its nickel(II) metallated derivative exhibit moderate cytotoxicity toward cells in culture. Strikingly, the nickel porphyrin derivative was able to displace hPOT1 shelterin protein from telomeres in human cells. Nickel(II) guanidinium phenyl porphyrin, a cationic bulky porphyrin is a powerful specific G-quadruplex DNA ligand. It enters the cells and induces shelterin modification.
authors.affiliation: Centre National de la Recherche Scientifique, Laboratoire de Chimie de Coordination, 205 Route de Narbonne, 31077, Toulouse, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Sabater
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Nicolau-Travers
authors.forename: Aurore
authors.initials: A
authors.lastname: De Rache
authors.forename: Enora
authors.initials: E
authors.lastname: Prado
authors.forename: Jérôme
authors.initials: J
authors.lastname: Dejeu
authors.forename: Oriane
authors.initials: O
authors.lastname: Bombarde
authors.forename: Joris
authors.initials: J
authors.lastname: Lacroix
authors.forename: Patrick
authors.initials: P
authors.lastname: Calsou
authors.forename: Eric
authors.initials: E
authors.lastname: Defrancq
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mergny
authors.forename: Dennis
authors.initials: D
authors.lastname: Gomez
authors.forename: Geneviève
authors.initials: G
authors.lastname: Pratviel
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002942:Circular Dichroism; D003035:Cobalt / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes / Q000187:drug effects*; D019791:Guanidine / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D008665:Metalloporphyrins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009532:Nickel / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry*; D021381:Protein Transport / Q000187:drug effects; D000089804:Shelterin Complex; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance; D016615:Telomere / Q000187:drug effects*; D034501:Telomere-Binding Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D008024:Ligands; D008665:Metalloporphyrins; C440849:POT1 protein, human; D011166:Porphyrins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D003035:Cobalt; D009532:Nickel; D019791:Guanidine
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