Unknown

Dataset Information

0

Extracellular palladium-catalysed dealkylation of 5-fluoro-1-propargyl-uracil as a bioorthogonally activated prodrug approach.


ABSTRACT: A bioorthogonal organometallic reaction is a biocompatible transformation undergone by a synthetic material exclusively through the mediation of a non-biotic metal source; a selective process used to label biomolecules and activate probes in biological environs. Here we report the in vitro bioorthogonal generation of 5-fluorouracil from a biologically inert precursor by heterogeneous Pd(0) catalysis. Although independently harmless, combined treatment of 5-fluoro-1-propargyl-uracil and Pd(0)-functionalized resins exhibits comparable antiproliferative properties to the unmodified drug in colorectal and pancreatic cancer cells. Live-cell imaging and immunoassay studies demonstrate that the cytotoxic activity of the prodrug/Pd(0)-resin combination is due to the in situ generation of 5-fluorouracil. Pd(0)-resins can be carefully implanted in the yolk sac of zebrafish embryos and display excellent biocompatibility and local catalytic activity. The in vitro efficacy shown by this masking/activation strategy underlines its potential to develop a bioorthogonally activated prodrug approach and supports further in vivo investigations.

SUBMITTER: Weiss JT 

PROVIDER: S-EPMC3929780 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

altmetric image

Publications

Extracellular palladium-catalysed dealkylation of 5-fluoro-1-propargyl-uracil as a bioorthogonally activated prodrug approach.

Weiss Jason T JT   Dawson John C JC   Macleod Kenneth G KG   Rybski Witold W   Fraser Craig C   Torres-Sánchez Carmen C   Patton E Elizabeth EE   Bradley Mark M   Carragher Neil O NO   Unciti-Broceta Asier A  

Nature communications 20140101


A bioorthogonal organometallic reaction is a biocompatible transformation undergone by a synthetic material exclusively through the mediation of a non-biotic metal source; a selective process used to label biomolecules and activate probes in biological environs. Here we report the in vitro bioorthogonal generation of 5-fluorouracil from a biologically inert precursor by heterogeneous Pd(0) catalysis. Although independently harmless, combined treatment of 5-fluoro-1-propargyl-uracil and Pd(0)-fun  ...[more]

Similar Datasets

| S-EPMC4365405 | biostudies-literature
| S-EPMC5705238 | biostudies-literature
| S-EPMC6092016 | biostudies-literature
| S-EPMC5355892 | biostudies-literature
| S-EPMC3353771 | biostudies-literature
| S-EPMC5082708 | biostudies-literature
| S-EPMC8004868 | biostudies-literature
| S-EPMC8159216 | biostudies-literature
| S-EPMC6268340 | biostudies-literature
| S-EPMC5548382 | biostudies-literature