Photocontrolled Binding of Styrylnaphthyridine Ligands to Abasic Site-Containing DNA by Reversible [2+2] Cycloaddition and Cycloreversion.
Chemistry
; 30(31): e202400423, 2024 Jun 03.
Article
em En
| MEDLINE
| ID: mdl-38545937
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 0.5-8.4×104â
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 420â
nm the photodimer is formed, which does not bind to AP-DNA. In turn, the naphthyridine is regained with excitation at 315â
nm. Most notably, this photoinduced deactivation and release of the DNA ligand can be performed inâ
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Reação de Cicloadição
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Naftiridinas
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article