Citation Link: https://doi.org/10.1002/chem.202400423
Photocontrolled Binding of Styrylnaphthyridine Ligands to Abasic Site‐Containing DNA by Reversible [2+2] Cycloaddition and Cycloreversion
Publication Type
Article
Author(s)
Subjects
DNA
Chemistry
AP site
Titration
Ligand (biochemistry)
Biophysics
Combinatorial chemistry
Cycloaddition
Stereochemistry
Photochemistry
DNA damage
Biochemistry
Biology
Receptor
Catalysis
Organic chemistry
Date Issued
2024
Abstract
Five novel styrylnaphthyridine derivatives were synthesized and shown to operate as photoswitchable, selective ligands for abasic site‐containing DNA (AP‐DNA), which is an important therapeutic and diagnostic target. These compounds associate with AP‐DNA with binding constants of 0.5–8.4×10 4 M −1 as shown by photometric and fluorimetric titrations. Specifically, these ligands bind preferentially to AP‐DNA relative to regularly paired duplex DNA. As a special feature, the association of these ligands with DNA can be controlled by means of a reversible [2+2] photocycloaddition. Upon irradiation at 420 nm the photodimer is formed, which does not bind to AP‐DNA. In turn, the naphthyridine is regained with excitation at 315 nm. Most notably, this photoinduced deactivation and release of the DNA ligand can be performed in situ in the presence of AP‐DNA, thus providing a tool for on‐demand delivery of a DNA binder. Overall, these results provide a promising starting point for the development of functional AP‐DNA ligands whose bioactivity can be modulated by light with local and temporal control.
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