Drug "Clicking" on Cell-Penetrating Fluorescent Nanoparticles for In Cellulo Chemical Proteomics.
Bioconjug Chem
; 29(9): 3154-3160, 2018 09 19.
Article
en En
| MEDLINE
| ID: mdl-30122043
ABSTRACT
Chemical proteomics approaches are widely used to identify molecular targets of existing or novel drugs. This manuscript describes the development of a straightforward approach to conjugate azide-labeled drugs via click chemistry to alkyne-tagged cell-penetrating fluorescent nanoparticles as a novel tool to study target engagement and/or identification inside living cells. A modification of the Baeyer test for alkynes allows monitoring the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, guaranteeing the presence of the drug on the solid support. As a proof of concept, the conjugation of the promiscuous kinase inhibitor dasatinib to Cy5-labeled nanoparticles is presented. Dasatinib-decorated fluorescent nanoparticles efficiently inhibited its protein target SRC in vitro, entered cancer cells, and colocalized with SRC in cellulo.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Permeabilidad de la Membrana Celular
/
Proteómica
/
Nanopartículas
/
Colorantes Fluorescentes
Límite:
Humans
Idioma:
En
Revista:
Bioconjug Chem
Asunto de la revista:
BIOQUIMICA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Reino Unido