Specific Recognition of G-Quadruplexes Over Duplex-DNA by a Macromolecular NIR Two-Photon Fluorescent Probe.
Marco DeianaBastien MettraLara Martinez-FernandezLeszek M MazurKrzysztof PawlikChantal AndraudMarek SamocRoberto ImprotaCyrille MonnereauKatarzyna MatczyszynPublished in: The journal of physical chemistry letters (2017)
The implication of guanine-rich DNA sequences in biologically important roles such as telomerase dysfunction and the regulation of gene expression has prompted the search for structure-specific G-quadruplex agents for targeted diagnostic and 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, the striking changes in its linear and third-order nonlinear optical properties, combined with the emergence of a strong induced electronic circular dichroism (ECD) signal upon binding to canonical and noncanonical DNA secondary structures allowed for a highly specific detection of several different G4s. Furthermore, through a detailed computational analysis we bring compelling evidence that our probe intercalation within G4s is a thermodynamically favored event, and we fully rationalize the spectroscopic evolution resulting from this complexation event by providing a reasonable explanation regarding the origin of the peculiar ECD effect that accompanies it.
Keyphrases
- living cells
- fluorescent probe
- circulating tumor
- single molecule
- cell free
- gene expression
- nucleic acid
- photodynamic therapy
- circulating tumor cells
- high resolution
- oxidative stress
- molecular docking
- drug delivery
- high glucose
- fluorescence imaging
- drug release
- genome wide
- mass spectrometry
- quantum dots
- endothelial cells
- neural network
- label free