Elliott, T.S. et al. Cell Chem. Biol. 23, 805–815 (2016).

In order to effectively study differentiated cell and tissue function, it is necessary to use approaches that target specific cell types. Elliott et al. describe stochastic orthogonal recoding of translation with enrichment (SORT-E), a method for cotranslationally tagging specific, genetically targeted cell proteomes using a cyclopropene-containing unnatural amino acid that is incorporated in response to diverse codons. A tetrazine–biotin probe is covalently conjugated to the cyclopropene-based amino acid, enabling the enrichment of tagged proteins via streptavidin affinity resin, which is then followed by mass spectrometry analysis for protein identification. The authors applied the method to identify newly synthesized proteins in Drosophila melanogaster ovary germ cells. The approach should be particularly useful for following cell-specific proteomes during development or disease progression.