RT Journal Article
T1 Drug "Clicking" on Cell-Penetrating Fluorescent Nanoparticles for In Cellulo Chemical Proteomics.
A1 Valero, Teresa
A1 Delgado-González, Antonio
A1 Unciti-Broceta, Juan Diego
A1 Cano-Cortés, Victoria
A1 Pérez-López, Ana M
A1 Unciti-Broceta, Asier
A1 Sánchez Martín, Rosario M
AB 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.
YR 2018
FD 2018-09-04
LK http://hdl.handle.net/10668/12851
UL http://hdl.handle.net/10668/12851
LA en
DS RISalud
RD Apr 9, 2025