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Proc Natl Acad Sci U S A. 2019 Apr 23;116(17):8155-8160. doi: 10.1073/pnas.1821151116. Epub 2019 Apr 10.

TePhe, a tellurium-containing phenylalanine mimic, allows monitoring of protein synthesis in vivo with mass cytometry.

Author information

1
Department of Chemistry, University of Toronto, Toronto, ON, Canada M5S 3H6.
2
The Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada M5T 2M9.
3
Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada M5S 3E2.
4
Department of Chemistry, University of Toronto, Toronto, ON, Canada M5S 3H6; mark.nitz@utoronto.ca.

Abstract

Protein synthesis is central to maintaining cellular homeostasis and its study is critical to understanding the function and dysfunction of eukaryotic systems. Here we report L-2-tellurienylalanine (TePhe) as a noncanonical amino acid for direct measurement of protein synthesis. TePhe is synthetically accessible, nontoxic, stable under biological conditions, and the tellurium atom allows its direct detection with mass cytometry, without postexperiment labeling. TePhe labeling is competitive with phenylalanine but not other large and aromatic amino acids, demonstrating its molecular specificity as a phenylalanine mimic; labeling is also abrogated in vitro and in vivo by the protein synthesis inhibitor cycloheximide, validating TePhe as a translation reporter. In vivo, imaging mass cytometry with TePhe visualizes translation dynamics in the mouse gut, brain, and tumor. The strong performance of TePhe as a probe for protein synthesis, coupled with the operational simplicity of its use, suggests TePhe could become a broadly applied molecule for measuring translation in vitro and in vivo.

KEYWORDS:

mass cytometry; protein synthesis; tellurium

PMID:
30971489
PMCID:
PMC6486722
[Available on 2019-10-10]
DOI:
10.1073/pnas.1821151116

Conflict of interest statement

Conflict of interest statement: L.M.W., R.N.V., L.J.E., B.G.W., and M.N. have pending intellectual property on the use of tellurium reagents for mass cytometry applications which has been licensed to the Fluidigm Canada.

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