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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 116; no. 17; pp. 8155 - 8160
• Main Authors: Bassan, Jay, Willis, Lisa M., Vellanki, Ravi N., Nguyen, Alan, Edgar, Landon J., Wouters, Bradly G., Nitz, Mark
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 23.04.2019
• Subjects: Amino acids; Amino Acids - chemistry; Amino Acids - metabolism; Animals; Biological Sciences; Brain; Brain - diagnostic imaging; Brain - metabolism; Brain tumors; Cycloheximide; Cycloheximide - pharmacology; Cytometry; Flow Cytometry - methods; HCT116 Cells; Homeostasis; Humans; Image Cytometry - methods; Jejunum - diagnostic imaging; Jejunum - metabolism; Jurkat Cells; Labeling; Mice; Neoplasms, Experimental; Neuroimaging; Phenylalanine; Phenylalanine - chemistry; Phenylalanine - metabolism; Physical Sciences; Protein biosynthesis; Protein Biosynthesis - drug effects; Protein Biosynthesis - physiology; Protein synthesis; Protein Synthesis Inhibitors - pharmacology; Proteins; Tellurium; Tellurium - chemistry; Tellurium - metabolism; Translation; tellurium; protein synthesis; mass cytometry
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1821151116

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.