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

Bioorg Med Chem Lett. 2016 Feb 15;26(4):1333-6. doi: 10.1016/j.bmcl.2015.12.079. Epub 2015 Dec 22.


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.

Keywords: Click chemistry; Post-translational modification; Protein farnesylation; Protein prenylation; Substrate analogs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkyl and Aryl Transferases / metabolism*
  • Alkynes / chemistry
  • Click Chemistry
  • Kinetics
  • Peptides / chemistry
  • Peptides / metabolism
  • Polyisoprenyl Phosphates / chemistry
  • Polyisoprenyl Phosphates / metabolism*
  • Protein Prenylation
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / metabolism*
  • Substrate Specificity


  • Alkynes
  • Peptides
  • Polyisoprenyl Phosphates
  • Sesquiterpenes
  • farnesyl pyrophosphate
  • Alkyl and Aryl Transferases
  • p21(ras) farnesyl-protein transferase