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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

  • Laurent Sabater
  • Marie-Laure Nicolau-Travers
  • Aurore De Rache
  • Enora Prado
  • Jérôme Dejeu
  • Oriane Bombarde
  • Joris Lacroix
  • Patrick Calsou
  • Eric Defrancq
  • Jean-Louis Mergny
  • Dennis Gomez
  • Geneviève PratvielEmail author
Original Paper

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.

Keywords

G4 ligand Telomere Porphyrin G-quadruplex POT1 

Notes

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.

Supplementary material

775_2015_1260_MOESM1_ESM.pdf (953 kb)
Supplementary material 1 (PDF 952 kb)

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Copyright information

© SBIC 2015

Authors and Affiliations

  • Laurent Sabater
    • 1
    • 2
  • Marie-Laure Nicolau-Travers
    • 3
    • 4
  • Aurore De Rache
    • 6
    • 7
  • Enora Prado
    • 5
  • Jérôme Dejeu
    • 5
  • Oriane Bombarde
    • 3
    • 4
  • Joris Lacroix
    • 1
    • 2
  • Patrick Calsou
    • 3
    • 4
  • Eric Defrancq
    • 5
  • Jean-Louis Mergny
    • 6
    • 7
  • Dennis Gomez
    • 3
    • 4
  • Geneviève Pratviel
    • 1
    • 2
    Email author
  1. 1.Centre National de la Recherche Scientifique, Laboratoire de Chimie de CoordinationToulouseFrance
  2. 2.Université de ToulouseToulouseFrance
  3. 3.Centre National de la Recherche ScientifiqueInstitut de Pharmacologie et de Biologie StructuraleToulouse Cedex 4France
  4. 4.Institut de Pharmacologie et de Biologie StructuraleUniversité de Toulouse-Université Paul SabatierToulouseFrance
  5. 5.Université Grenoble Alpes, DCMGrenobleFrance
  6. 6.Laboratoire ARNAUniversité de Bordeaux33000France
  7. 7.INSERM U869, Institut Européen de Chimie et BiologiePessacFrance

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