Evaluation of an alkyne-containing analogue of farnesyl diphosphate as a dual substrate for protein-prenyltransferases

Ayako Hosokawa, James W. Wollack, Zhiyuan Zhang, Lin Chen, George Barany, Mark D. Distefano

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


The development of tools for proteomic analysis is an active area of research. Here, we report on the synthesis of 12-propargoxyfarnesyl diphosphate (1), an alkyne-containing analogue of farnesyl diphosphate (FPP), and its enzymatic incorporation into peptide substrates by both protein- farnesyltransferase (PFTase) and protein-geranylgeranyltransferase type I (PGGTase-I). Compound 1 was prepared from farnesol in 6 steps. Kinetic analyses indicate that 1 is incorporated into cognate peptide substrates by PFTase or PGGTase at concentrations and rates comparable to those of the natural lipid substrates for these enzymes, and mass spectrometric analyses proved the structures of the prenylated peptide products. Incubation of 1 in the presence of PFTase and PGGTase peptide substrates, and the cognate transferases, results in the simultaneous prenylation of both peptides emphasizing the dual substrate nature of 1. Thus, because 1 is a substrate for both enzymes, it can be used to introduce alkyne functionality into proteins that are normally either farnesylated or geranylgeranylated. This approach should be useful for a broad range of applications ranging from selective protein labeling to proteomic analysis.

Original languageEnglish (US)
Pages (from-to)345-354
Number of pages10
JournalInternational Journal of Peptide Research and Therapeutics
Issue number1-2
StatePublished - Jun 2007


  • Alkyne
  • Farnesyltransferase
  • Geranylgeranyltransferase
  • Peptide modification
  • Prenylated peptide

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