Preferential targeting of i-motifs and G-quadruplexes by small molecules. Issue 11 (19th September 2017)

• Record Type: Journal Article
• Authors: Debnath, Manish; Ghosh, Shirsendu; Chauhan, Ajay; Paul, Rakesh; Bhattacharyya, Kankan; Dash, Jyotirmayee
• Is Part Of: Chemical science. Volume 8:Issue 11(2017)
• Page Start: 7448
• Page End: 7456
• Publication Date: 2017-09-19
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c7sc02693e
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : Ligand-dependent regulation of gene expression has been delineated by targeting i-motifs and G-quadruplexes. 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 andPBP2 ) 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 -isomerPBP2 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 thatPBP1 upregulates andPBP2 downregulates BCL-2 gene expression in cancer cells.