Exploring the preferential interaction of quercetin with VEGF promoter G-quadruplex DNA and construction of a pH-dependent DNA-based logic gate

Abstract

G-Quadruplex DNA (G4–DNA) is one of the most important non-canonical nucleic acid structures. G4–DNA forming sequences are present in different crucial genomic regions and are abundant in promoter regions of several oncogenes. Therefore, G4–DNA is an important target for anticancer drugs and hence binding interactions between G4–DNA and small molecule ligands are of great importance. Since G4–DNA is a highly polymorphic structure, it is important to identify ligand molecules which preferentially target a particular quadruplex sequence in comparison to other quadruplexes. In the present study, different spectroscopic techniques have been used to explore the interaction of the dietary plant flavonoid quercetin (Que) with various G4–DNA structures (VEGF, c-MYC, c-KIT1, c-KIT2, h-TELO) along with double stranded (duplex) DNA. We found that Que shows preferential interaction with VEGF G4–DNA compared to other G4–DNA structures as well as duplex DNA. This identifies Que as an appropriate natural product based ligand for targeting VEGF G4–DNA. We also observed pH dependent interaction of Que with VEGF G4–DNA, based on which we have designed a complex Boolean logic gate exploiting Que as a sensing molecule.