Chemical proteomic approaches to investigate S-prenylation

Protein S-prenylation is a post-translational lipid modification that occurs at C-terminal cysteines. While S-prenylation has been widely studied in the context of disease biology and drug discovery, only in the last decade have robust proteomic techniques emerged to study the complex dynamics between different classes of protein prenyltransferases, significantly aiding the development and application of tools and inhibitors. Herein, we describe the use of S-prenylation probes as a chemical proteomic technique to interrogate S-geranylgeranylation and S-farnesylation, the two classes of protein prenylation, from sample preparation to mass spectrometry analysis.