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

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 pe...

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Bibliographic Details
Published inbioRxiv
Main Authors Francesco Rota Sperti, Charbonnier, Thibaut, Lejault, Pauline, Zell, Joanna, Bernhard, Claire, Valverde, Ibai E, Monchaud, David
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 18.12.2020
Subjects
Avidin
Biotin
Cell fate
Gene expression
Genomes
Ligands
Transcriptomes
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Summary: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. Figure1 Figure1 * Download figure * Open in new tab Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2020.12.18.422878