Premium
Fluorescent Dansyl‐Guanosine Conjugates that Bind c‐MYC Promoter G‐Quadruplex and Downregulate c‐MYC Expression
Author(s) -
Pavan Kumar Y.,
Saha Puja,
Saha Dhurjhoti,
Bessi Irene,
Schwalbe Harald,
Chowdhury Shantanu,
Dash Jyotirmayee
Publication year - 2016
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201500631
Subject(s) - g quadruplex , guanosine , chemistry , electrophoretic mobility shift assay , dna , microbiology and biotechnology , oligonucleotide , biochemistry , dansyl chloride , transcription factor , biology , derivatization , gene , high performance liquid chromatography , chromatography
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.