Specific Recognition of G-Quadruplexes Over Duplex-DNA by a Macromolecular NIR Two-Photon Fluorescent Probe

• DOI: 10.1021/acs.jpclett.7b02547
• Publication Date: 2017-11-17T22:27:16Z
• Authors: Marco Deiana; Bastien Mettra; Lara Martinez-Fer...; Leszek M. Mazur; Krzysztof Pawlik; Chantal Andraud; Marek Samoc; Roberto Improta; Cyrille Monnereau; Katarzyna Matczyszyn
• Keywords: G-quadruplex; Duplex (building)

The implication of guanine-rich DNA sequences in biologically important roles such as telomerase dysfunction and the regulation gene expression has prompted search for structure-specific G-quadruplex agents targeted diagnostic therapeutic applications. Herein, we report on a near-infrared (NIR) two-photon poly(cationic) anthracene-based macromolecule able to selectively target G-quadruplexes (G4s) over genomic double-stranded DNA. In particular, striking changes its linear third-order nonlinear optical properties, combined with emergence strong induced electronic circular dichroism (ECD) signal upon binding canonical noncanonical secondary structures allowed highly specific detection several different G4s. Furthermore, through detailed computational analysis bring compelling evidence that our probe intercalation within G4s is thermodynamically favored event, fully rationalize spectroscopic evolution resulting from this complexation event by providing reasonable explanation regarding origin peculiar ECD effect accompanies it.