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Biomimetic, smart and multivalent ligands for G-quadruplex isolation and bioorthogonal imaging

Francesco Rota Sperti, Thibaut Charbonnier, Pauline Lejault, Joanna Zell, View ORCID ProfileClaire Bernhard, View ORCID ProfileIbai E. Valverde, View ORCID ProfileDavid Monchaud
doi: https://doi.org/10.1101/2020.12.18.422878
Francesco Rota Sperti
1ICMUB, CNRS UMR6302, UBFC Dijon, 9, Avenue Alain Savary, 21078 Dijon, France
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Thibaut Charbonnier
1ICMUB, CNRS UMR6302, UBFC Dijon, 9, Avenue Alain Savary, 21078 Dijon, France
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Pauline Lejault
1ICMUB, CNRS UMR6302, UBFC Dijon, 9, Avenue Alain Savary, 21078 Dijon, France
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Joanna Zell
1ICMUB, CNRS UMR6302, UBFC Dijon, 9, Avenue Alain Savary, 21078 Dijon, France
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Claire Bernhard
1ICMUB, CNRS UMR6302, UBFC Dijon, 9, Avenue Alain Savary, 21078 Dijon, France
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  • ORCID record for Claire Bernhard
Ibai E. Valverde
1ICMUB, CNRS UMR6302, UBFC Dijon, 9, Avenue Alain Savary, 21078 Dijon, France
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  • ORCID record for Ibai E. Valverde
  • For correspondence: ibai.valverde@u-bourgogne.fr david.monchaud@cnrs.fr
David Monchaud
1ICMUB, CNRS UMR6302, UBFC Dijon, 9, Avenue Alain Savary, 21078 Dijon, France
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  • ORCID record for David Monchaud
  • For correspondence: ibai.valverde@u-bourgogne.fr david.monchaud@cnrs.fr
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Abstract

G-quadruplexes (G4s) continue to gather wide attention in the field of chemical biology as their prevalence in the human genome and transcriptome strongly suggests that they may play key regulatory roles in cell biology. G4-specific, cell-permeable small molecules (G4-ligands) innovately permit the interrogation of cellular circuitries in order to assess to what extent G4s influence cell fate and functions. Here, we report on multivalent, biomimetic G4-ligands referred to as TASQs that enable both the isolation and visualization of G4s in human cells. Two biotinylated TASQs, BioTASQ and BioCyTASQ, are indeed efficient molecular tools to fish out G4s of mixtures of nucleic acids through simple affinity capture protocols and to image G4s in cells via a biotin/avidin pretargeted imaging system first applied here to G4s, found to be a reliable alternative to in situ click chemistry.

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Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted December 18, 2020.
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Biomimetic, smart and multivalent ligands for G-quadruplex isolation and bioorthogonal imaging
Francesco Rota Sperti, Thibaut Charbonnier, Pauline Lejault, Joanna Zell, Claire Bernhard, Ibai E. Valverde, David Monchaud
bioRxiv 2020.12.18.422878; doi: https://doi.org/10.1101/2020.12.18.422878
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Biomimetic, smart and multivalent ligands for G-quadruplex isolation and bioorthogonal imaging
Francesco Rota Sperti, Thibaut Charbonnier, Pauline Lejault, Joanna Zell, Claire Bernhard, Ibai E. Valverde, David Monchaud
bioRxiv 2020.12.18.422878; doi: https://doi.org/10.1101/2020.12.18.422878

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