Issue 11, 2017

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


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

Supplementary files

Article information

Article type
Edge Article
16 Jun 2017
07 Sep 2017
First published
08 Sep 2017
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2017,8, 7448-7456

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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