Bridged Azobenzene Exhibits Fully Reversible Photocontrolled Binding to a G‑Quadruplex DNA/Duplex Junction
The ability to selectively control DNA conformation using light as an external stimulus offers unique opportunities to control specific DNA sequences in biological settings and to develop nucleotide-based nanodevices. We describe a duplex/G-quadruplex (G4) junction-binding chemotype derived from a c...
| Autores: | , , , , , , , , , |
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| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Recursos: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/399761 |
| Acesso em linha: | http://hdl.handle.net/10261/399761 https://api.elsevier.com/content/abstract/scopus_id/105014787554 |
| Access Level: | acceso abierto |
| Palavra-chave: | Supramolecular DNA interactions DNA nanodevices G4/duplex DNA junction Azobenzene Photoswitch DNA |
| Resumo: | The ability to selectively control DNA conformation using light as an external stimulus offers unique opportunities to control specific DNA sequences in biological settings and to develop nucleotide-based nanodevices. We describe a duplex/G-quadruplex (G4) junction-binding chemotype derived from a cyclic azobenzene core that reversibly photoswitches between cis and trans isomers, mediated exclusively by visible light under physiological conditions. We demonstrate the selective binding of the elongated trans conformation, with over 50-fold higher affinity, toward LTR-III G4 (an important HIV-1 sequence), and show that binding and dissociation from the LTR-III G4 can be controlled reversibly by alternate irradiation with low-intensity blue and green light. NMR and MD simulations indicate that the different isomers exhibit very distinct binding modes. While the elongated trans ligand preferentially binds at the G4/duplex junction of the LTR-III sequence, a DNA motif which is gaining increasing attention as a potential drug target, the bent cis isomer favors the duplex region. |
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