Protein prenylation is an essential post-translational modification of proteins where isoprenoids farnesyl (C15) and geranylgeranyl (C20) isoprenoids are attached to their C-termini. This pathway has been extensively studied using chemical probes in both in vitro and in vivo investigations (e.g. in live cells). Metabolic labeling strategies often use statins, inhibitors of hydroxymethylglutaryl coenzyme A (HMG-CoA), to enhance probe incorporation. However, the effectiveness of these different statins has not been explored. This research project is focused on studying the effect of statins in enhancing the incorporation of two C15 alkyne probes (C15-Alk-OPP and C15-Alk-OH) into prenylated proteins in Hela and Cos 7 cell lines. Metabolic labeling of such probes in the presence of statins, followed by click reaction with TAMRA-N3 allows visualization of the extent of labeling of each statin. Among the statins tested, fluvastatin, lovastatin, and simvastatin showed the most improved labeling at higher concentrations, particularly on the putative small GTPases that migrate in the 25 kDa region of an SDS PAGE gel.

Exploring the differences among statins in enhancing the metabolic labeling of prenylated proteins using isoprenoid probes

2019 Spring National Meeting

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