Photoreactive Molecular Glue for Enhancing the Efficacy of DNA Aptamers by Temporary-to-Permanent Conjugation with Target Proteins.
J Am Chem Soc
; 143(34): 13937-13943, 2021 09 01.
Article
en En
| MEDLINE
| ID: mdl-34424707
ABSTRACT
We developed a photoreactive molecular glue, BPGlue-N3, which can provide a universal strategy to enhance the efficacy of DNA aptamers by temporary-to-permanent stepwise stabilization of their conjugates with target proteins. As a proof-of-concept study, we applied BPGlue-N3 to the SL1 (DNA aptamer)/c-Met (target protein) conjugate system. BPGlue-N3 can adhere to and temporarily stabilize this aptamer/protein conjugate multivalently using its guanidinium ion (Gu+) pendants that form a salt bridge with oxyanionic moieties (e.g., carboxylate and phosphate) and benzophenone (BP) group that is highly affinitive to DNA duplexes. BPGlue-N3 is designed to carry a dual-mode photoreactivity; upon exposure to UV light, the temporarily stabilized aptamer/protein conjugate reacts with the photoexcited BP unit of adhering BPGlue-N3 and also a nitrene species, possibly generated by the BP-to-N3 energy transfer in BPGlue-N3. We confirmed that SL1, covalently conjugated with c-Met, hampered the binding of hepatocyte growth factor (HGF) onto c-Met, even when the SL1/c-Met conjugate was rinsed prior to the treatment with HGF, and suppressed cell migration caused by HGF-induced c-Met phosphorylation.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Proteínas Proto-Oncogénicas c-met
/
Aptámeros de Nucleótidos
Límite:
Humans
Idioma:
En
Revista:
J Am Chem Soc
Año:
2021
Tipo del documento:
Article
País de afiliación:
Japón