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

Autor: Schlosser J; Department of Chemistry and Biology, and Center of Micro- and Nanochemistry and (Bio)Technology (Cμ), University of Siegen, Adolf-Reichwein Str. 2, 57068, Siegen, Germany., Ihmels H; Department of Chemistry and Biology, and Center of Micro- and Nanochemistry and (Bio)Technology (Cμ), University of Siegen, Adolf-Reichwein Str. 2, 57068, Siegen, Germany.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2024 Jun 03; Vol. 30 (31), pp. e202400423. Date of Electronic Publication: 2024 Apr 23.
DOI: 10.1002/chem.202400423
Abstrakt: 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.
(© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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