Fluorescence Quenching Dynamics of 2-Amino-7-methyl-1,8-naphthyridine in Abasic-Site-Containing DNA Duplexes for Nucleobase Recognition

Abstract

Dramatic fluorescence quenching of small heterocyclic ligands trapped in the abasic site (AP) of DNA has been implemented as an unprecedented strategy recognizing single-base mutations in sequence analysis of cancer genes. However, the key mechanisms governing selective nucleobase recognition remain to be disentangled. Herein, we perform fluorescence quenching dynamics studies for 2-amino-7-methyl-1,8-naphthyridine (AMND) in well-designed AP-containing DNA single/double strands. The primary mechanism is discovered, showing that AMND only targets cytosine to form a pseudo-base pair, and therefore, fluorescence quenching of AMND arises through the DNA-mediated electron transfer (ET) between excited state AMND* and flanking nucleobases, most favorably with flanking guanines. Subtle dynamic conformational variations induced by different flanking nucleobases are revealed and found to modulate efficiencies of electron transfer and fluorescence quenching. These findings provide critical mechanistic insights for guiding the design of photoinduced electron transfer (PET)-based fluorescent ligands as sensitive singlebase recognition reporters.

Photocontrolled Binding of Styrylnaphthyridine Ligands to Abasic Site‐Containing DNA by Reversible [2+2] Cycloaddition and Cycloreversion

“…In order to extend the toolbox of selective AP‐DNA ligands we proposed to furnish an established ligand system with a photoswitchable unit, which in turn should allow for an improved selective binding process by means of controlled irradiation. We chose the naphthyridine unit as building block, because derivatives thereof have been shown to be suitable AP‐DNA‐targeting ligands which bind with reasonable affinity and selectivity to AP sites by hydrogen‐bond interactions with the opposing DNA base [5,7,25,26] . As photocontrollable unit, the styryl chromophore should be attached to the naphthyridine, resulting in a stilbene‐type photochromic system.…”