Bassan J,
Willis LM,
Vellanki RN,
Nguyen A,
Edgar LJ,
Wouters BG,
Nitz M.
* University of Toronto and University Health Network, Toronto, Canada
TePhe, A Tellurium-Containing Phenylalanine Mimic, Allows Monitoring of Protein Synthesis
in Vivo with Mass Cytometry.
Proc. Natl. Acad. Sci. U. S. A. 2019;
116: 8155-8160
Key words
mass cytometry - protein synthesis - tellurium - imaging mass cytometry
Significance
Protein translation is a dynamic process that is challenging to monitor in vivo; however,
competitive incorporation of unnatural amino acids is one way to introduce a probe
for detection. Imaging mass cytometry (IMC) is an imaging technique that follows a
similar workflow as immunofluorescence imaging. It uses a mass-tag instead of a fluorescent
dye for detection and does not require post-translational modification. The geometric
properties of tellurophene make the unnatural amino acid TePhe an excellent isostere
of phenylalanine.
Comment
TePhe is a non-toxic small-molecule probe that can be used to measure and visualize
protein translation both in vitro and in vivo. Exploiting the native translation machinery,
TePhe is competitively incorporated into proteins without the need for phenylalanine
starvation. Using IMC, protein synthesis in mice (gut, brain and tumor) was monitored
with spatiotemporal precision. Tellurium isotope enrichment enables multi-channel
observations. Additionally, this tellurium-containing probe has also high potential
for use in NMR spectroscopy or X-ray crystallography.
