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Issue 11, 2017
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Preferential targeting of i-motifs and G-quadruplexes by small molecules

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Abstract

i-Motifs and G-quadruplexes are dynamic nucleic acid secondary structures, which are believed to play key roles in gene expression. We herein report two peptidomimetic ligands (PBP1 and PBP2) that selectively target i-motifs and G-quadruplexes over double-stranded DNA. These peptidomimetics, regioisomeric with respect to the position of triazole/prolinamide motifs, have been synthesized using a modular method involving Cu(I)-catalyzed azide and alkyne cycloaddition. The para-isomer, PBP1 exhibits high selectivity for i-motifs while the meta-isomer PBP2 binds selectively to G-quadruplex structures. Interestingly, these ligands have the ability to induce G-quadruplex or i-motif structures from the unstructured single-stranded DNA conformations, as observed using single molecule Förster resonance energy transfer (smFRET) studies. The quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and dual-luciferase assays indicate that PBP1 upregulates and PBP2 downregulates BCL-2 gene expression in cancer cells.

Graphical abstract: Preferential targeting of i-motifs and G-quadruplexes by small molecules

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Publication details

The article was received on 16 Jun 2017, accepted on 07 Sep 2017 and first published on 08 Sep 2017


Article type: Edge Article
DOI: 10.1039/C7SC02693E
Citation: Chem. Sci., 2017,8, 7448-7456
  • Open access: Creative Commons BY license
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    Preferential targeting of i-motifs and G-quadruplexes by small molecules

    M. Debnath, S. Ghosh, A. Chauhan, R. Paul, K. Bhattacharyya and J. Dash, Chem. Sci., 2017, 8, 7448
    DOI: 10.1039/C7SC02693E

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