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.
Pharmacology, Toxicology and Pharmaceutical Science
7
2%
Materials Science
5
2%
Other
25
8%
Unknown
58
19%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 205. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 July 2018.
All research outputs
#155,400
of 22,715,151 outputs
Outputs from Nature Communications
#2,221
of 46,756 outputs
Outputs of similar age
#1,587
of 313,366 outputs
Outputs of similar age from Nature Communications
#17
of 465 outputs
Altmetric has tracked 22,715,151 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 46,756 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 55.5. This one has done particularly well, scoring higher than 95% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 313,366 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 99% of its contemporaries.
We're also able to compare this research output to 465 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 96% of its contemporaries.
