Attempts to identify the prenyl-proteome of cells or changes in prenylation following drug treatment have used 'clickable' alkyne-modified analogs of the lipid substrates farnesyl- and geranylgeranyl-diphosphate (FPP and GGPP). We characterized the reactivity of four alkyne-containing analogs of FPP with purified protein farnesyltransferase and a small library of dansylated peptides using an in vitro continuous spectrofluorimetric assay. These analogs alter prenylation specificity and reactivity suggesting that in vivo results obtained using these FPP analogs should be interpreted cautiously.
Bibliographical noteFunding Information:
This work was supported by NIH grants F32GM112317 (B.C.J.), R01GM040602 (C.A.F.), R01CA078819 (R.A.G.), R01GM084152 (M.D.D.) and NSF grant CHE-1308655 (M.D.D.). We thank Andrew Placzek for providing analogs 2 and 3 . The authors publish this manuscript in memoriam to the late Richard Gibbs, who sadly passed away before its completion.
© 2015 Elsevier Ltd. All rights reserved.
- Click chemistry
- Post-translational modification
- Protein farnesylation
- Protein prenylation
- Substrate analogs