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Protein S -prenylation is a lipid modification that regulates membrane - protein and protein - protein interactions in cell aling. Herein, we report an alkynyl-isoprenol chemical reporter alk-FOH as an efficient substrate for prenyltransferases in mammalian cells that enables sensitive detection of S -farnesylated and S -geranylgeranylated proteins using bioorthogonal ligation methods. Fluorescent detection alleviates the need to deplete cellular isoprenoids for biochemical analysis of S -prenylated proteins and enables robust characterization of S -prenylated proteins , such as effectors that are injected into host cells by bacterial pathogens.

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