Fluorescent Dansyl-Guanosine Conjugates that Bindc-MYCPromoter G-Quadruplex and Downregulatec-MYCExpression

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 molecules that can inhibit the c-MYC promoter activity by stabilizing the c-MYC G-quadruplex could potentially be used as anticancer agents. In this context, we herein report synthesis of dansyl-guanosine conjugates using 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 visualization of c-MYC G-quadruplex over duplex DNA on gel electrophoresis. NMR spectroscopic titrations reveal the preferential binding sites of these dansyl ligands to the c-MYC G-quadruplex. A dual luciferase assay and qRT-PCR reveal that a dansyl-diguanosine represses the c-MYC expression, by possibly stabilizing the c-MYC G-quadruplex.