Interactions between Flavins and Quadruplex Nucleic Acids

Abstract

Quadruplex nucleic acids are widespread in genomes. They influence processes such as transcription, translation, replication, recombination, and the regulation of gene expression. Several synthetic ligands have been demonstrated to target quadruplex nucleic acids. However, only very few metabolites have been reported to interact with quadruplexes. In principle, an intracellular metabolite that selectively binds to four-stranded sequences could modulate quadruplex formation, stability, and thus functions in a riboswitch (or deoxyriboswitch) manner. Here we report quadruplex interactions with flavin derivatives such as FMN and FAD. The affinities were highest with parallel quadruplexes, with low (14-20 μm) dissociation constants. Taking into account combined intracellular flavin concentrations of 243 μm in E. coli, the observed interactions in principle open up the possibility of flavin levels affecting gene expression and other processes by modulating quadruplex formation. Not just a passing FAD: Quadruplex sequences are widespread in genomes, and although many quadruplex-targeting ligands have been synthesized, only very few metabolites have been reported to interact with them. We report G4 interactions with flavins such as FMN and FAD, thus opening the possibility of flavins affecting biological processes by modulating quadruplex formation.