Analogs of farnesyl diphosphate alter CaaX substrate specificity and reactions rates of protein farnesyltransferase

Benjamin C. Jennings, Amy M. Danowitz, Yen Chih Wang, Richard A. Gibbs, Mark D. Distefano, Carol A. Fierke

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1333-1336
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Issue number4
StatePublished - Feb 15 2016

Bibliographical note

Funding 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.

Publisher Copyright:
© 2015 Elsevier Ltd. All rights reserved.


  • Click chemistry
  • Post-translational modification
  • Protein farnesylation
  • Protein prenylation
  • Substrate analogs

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