Title |
Extracellular palladium-catalysed dealkylation of 5-fluoro-1-propargyl-uracil as a bioorthogonally activated prodrug approach
|
---|---|
Published in |
Nature Communications, February 2014
|
DOI | 10.1038/ncomms4277 |
Pubmed ID | |
Authors |
Jason T. Weiss, John C. Dawson, Kenneth G. Macleod, Witold Rybski, Craig Fraser, Carmen Torres-Sánchez, E. Elizabeth Patton, Mark Bradley, Neil O. Carragher, Asier Unciti-Broceta |
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. |
Twitter Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 4 | 57% |
Spain | 1 | 14% |
Unknown | 2 | 29% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 5 | 71% |
Science communicators (journalists, bloggers, editors) | 1 | 14% |
Scientists | 1 | 14% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
India | 2 | <1% |
Germany | 1 | <1% |
United Kingdom | 1 | <1% |
China | 1 | <1% |
United States | 1 | <1% |
Unknown | 287 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 70 | 24% |
Researcher | 44 | 15% |
Student > Master | 33 | 11% |
Student > Bachelor | 31 | 11% |
Other | 26 | 9% |
Other | 44 | 15% |
Unknown | 45 | 15% |
Readers by discipline | Count | As % |
---|---|---|
Chemistry | 144 | 49% |
Agricultural and Biological Sciences | 45 | 15% |
Biochemistry, Genetics and Molecular Biology | 16 | 5% |
Pharmacology, Toxicology and Pharmaceutical Science | 6 | 2% |
Materials Science | 5 | 2% |
Other | 27 | 9% |
Unknown | 50 | 17% |