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The nickel(II) complex of guanidinium phenyl porphyrin, a specific G-quadruplex ligand, targets telomeres and leads to POT1 mislocalization in culture cells

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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.

Graphical Abstract

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.

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Acknowledgments

We are grateful to Agence Nationale pour la Recherche (Quarpdiems grant ANR-12-BSV8-0008), Labex ARCANE (ANR-11-LABX-0003-01), Région Midi-Pyrénées, Région Aquitaine, Université Paul Sabatier, Toulouse for financial support. The authors acknowledge support from ICMG FR 2607 for providing synthesis and purification of oligonucleotides and SPR facilities.

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Authors and Affiliations

  1. Centre National de la Recherche Scientifique, Laboratoire de Chimie de Coordination, 205 Route de Narbonne, 31077, Toulouse, France

    Laurent Sabater, Joris Lacroix & Geneviève Pratviel

  2. Université de Toulouse, 31077, Toulouse, France

    Laurent Sabater, Joris Lacroix & Geneviève Pratviel

  3. Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, 205 Route de Narbonne, 31077, Toulouse Cedex 4, France

    Marie-Laure Nicolau-Travers, Oriane Bombarde, Patrick Calsou & Dennis Gomez

  4. Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse-Université Paul Sabatier, Toulouse, 31077, Cedex 4, France

    Marie-Laure Nicolau-Travers, Oriane Bombarde, Patrick Calsou & Dennis Gomez

  5. Université Grenoble Alpes, DCM, 38000, Grenoble, France

    Enora Prado, Jérôme Dejeu & Eric Defrancq

  6. Laboratoire ARNA, Université de Bordeaux, 33000, Bordeaux, France

    Aurore De Rache & Jean-Louis Mergny

  7. INSERM U869, Institut Européen de Chimie et Biologie, 2 rue Robert Escarpit, 33076, Pessac, France

    Aurore De Rache & Jean-Louis Mergny

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  1. Laurent Sabater
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  2. Marie-Laure Nicolau-Travers
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  12. Geneviève Pratviel
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Correspondence to Geneviève Pratviel.

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Sabater, L., Nicolau-Travers, ML., De Rache, A. et al. The nickel(II) complex of guanidinium phenyl porphyrin, a specific G-quadruplex ligand, targets telomeres and leads to POT1 mislocalization in culture cells. J Biol Inorg Chem 20, 729–738 (2015). https://doi.org/10.1007/s00775-015-1260-8

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  • DOI: https://doi.org/10.1007/s00775-015-1260-8

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