title: Fluorescent Dansyl-Guanosine Conjugates that Bind c-MYC Promoter G-Quadruplex and Downregulate c-MYC Expression.
abstract: The four-stranded G-quadruplex present in the c-MYC P1 promoter has been shown to play a pivotal role in the regulation of c-MYC transcription. Small-molecule compounds capable of inhibiting the c-MYC promoter activity by stabilising the c-MYC G-quadruplex could potentially be used as anticancer agents. In this context, here we report the synthesis of dansyl-guanosine conjugates through one-pot modular click reactions. The dansyl-guanosine conjugates can selectively detect c-MYC G-quadruplex over other biologically relevant quadruplexes and duplex DNA and can be useful as staining reagents for selective visualisation of c-MYC G-quadruplex over duplex DNA by gel electrophoresis. NMR spectroscopic titrations revealed the preferential binding sites of these dansyl ligands to the c-MYC G-quadruplex. A dual luciferase assay and qRT-PCR revealed that a dansyl-bisguanosine ligand represses the c-MYC expression, possibly by stabilising the c-MYC G-quadruplex.
authors.affiliation: Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur University, 2A ∞ B Raja S. C. Mullick Road, Jadavpur, Kolkata, 700032, India.
authors.forename: Y
authors.initials: Y
authors.lastname: Pavan Kumar
authors.affiliation: Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur University, 2A ∞ B Raja S. C. Mullick Road, Jadavpur, Kolkata, 700032, India.
authors.forename: Puja
authors.initials: P
authors.lastname: Saha
authors.affiliation: CSIR-Institute of Genomics and Integrative Biology, Mathura Road, Delhi, 110 025, India.
authors.forename: Dhurjhoti
authors.initials: D
authors.lastname: Saha
authors.affiliation: Institute of Organic Chemistry and Chemical Biology, Goethe University Frankfurt, and Center for Biomolecular Magnetic Resonance, Max-von-Laue Strasse 7, 60438, Frankfurt am Main, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Bessi
authors.affiliation: Institute of Organic Chemistry and Chemical Biology, Goethe University Frankfurt, and Center for Biomolecular Magnetic Resonance, Max-von-Laue Strasse 7, 60438, Frankfurt am Main, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Schwalbe
authors.affiliation: CSIR-Institute of Genomics and Integrative Biology, Mathura Road, Delhi, 110 025, India.
authors.forename: Shantanu
authors.initials: S
authors.lastname: Chowdhury
authors.affiliation: Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur University, 2A ∞ B Raja S. C. Mullick Road, Jadavpur, Kolkata, 700032, India. ocjd@iacs.res.in.
authors.forename: Jyotirmayee
authors.initials: J
authors.lastname: Dash
mesh_terms: D015536:Down-Regulation; D005456:Fluorescent Dyes / Q000737:chemistry*; D054856:G-Quadruplexes; D016259:Genes, myc; D006151:Guanosine / Q000737:chemistry*; D006801:Humans; D011401:Promoter Regions, Genetic
chemical_list: D005456:Fluorescent Dyes; D006151:Guanosine
keywords: G-quadruplexes; NMR spectroscopy; click chemistry; fluorescent probes; gel electrophoresis; transcription