%0 Journal Article
%A Valero, Teresa
%A Delgado-González, Antonio
%A Unciti-Broceta, Juan Diego
%A Cano-Cortés, Victoria
%A Pérez-López, Ana M
%A Unciti-Broceta, Asier
%A Sánchez Martín, Rosario M
%T Drug "Clicking" on Cell-Penetrating Fluorescent Nanoparticles for In Cellulo Chemical Proteomics.
%D 2018
%U http://hdl.handle.net/10668/12851
%X 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.
%~