Cationic red emitting fluorophore: A light up NIR fluorescent probe for G4-DNA

Publication date: Available online 11 October 2018

Source: Journal of Photochemistry and Photobiology B: Biology

Author(s): Beena Kumari, Akanksha Yadav, Sushree P. Pany, P.I. Pradeepkumar, Sriram Kanvah

Abstract

Guanine (G) quadruplexes (G4) are nucleic acid secondary structures formed by G-rich sequences, which are commonly found in human telomeric and oncogene-promoter regions, and they have emerged as targets for regulation of multiple biological processes. Considering their importance, targeting the G-quadruplex structure with small molecular binders is extremely pertinent. In this work, red emitting water soluble fluorophores bearing push-pull substituents were synthesized and examined for their interaction with human telomeric G4 and duplex (ds) DNAs. The presence of a strong electron donating (dimethylamino) and electron withdrawing (cationic pyridinium) groups linked through a conjugated double bond helps in water solubility and enabling the emission in the near IR region (>700–720 nm). Binding of this cationic dye to the G4-DNA yields multi-fold emission enhancement (~70 fold with G4-DNA vs. ~7 fold with ds-DNA) along with hypsochromic wavelength shifts (35 nm with G4-DNA and 8 nm with ds-DNA). The remarkable emission changes, ~2–4 fold enhanced binding efficiency noted with the antiparallel conformation of G4-DNA indicates preferential selectivity over ds-DNA. The molecular docking and dynamics studies of the ligands with duplex and interactions of the ligands with duplex and G4 DNA were performed, and they provide insights into the mode of binding of these dyes with G4-DNA and supplement the experimental observations.

Graphical Abstract