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 journalArticle

8 Citations (Scopus)

Abstract

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
Volume26
Issue number4
DOIs
StatePublished - Feb 15 2016

Fingerprint

Prenylation
Alkynes
Substrate Specificity
Reaction rates
Drug therapy
Peptide Library
Substrates
Proteome
Assays
Lipids
Peptides
Pharmaceutical Preparations
p21(ras) farnesyl-protein transferase
farnesyl pyrophosphate
geranylgeranyl pyrophosphate
In Vitro Techniques
prenyl

Keywords

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

Cite this

Analogs of farnesyl diphosphate alter CaaX substrate specificity and reactions rates of protein farnesyltransferase. / Jennings, Benjamin C.; Danowitz, Amy M.; Wang, Yen Chih; Gibbs, Richard A.; Distefano, Mark D; Fierke, Carol A.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 26, No. 4, 15.02.2016, p. 1333-1336.

Research output: Contribution to journalArticle

Jennings, Benjamin C. ; Danowitz, Amy M. ; Wang, Yen Chih ; Gibbs, Richard A. ; Distefano, Mark D ; Fierke, Carol A. / Analogs of farnesyl diphosphate alter CaaX substrate specificity and reactions rates of protein farnesyltransferase. In: Bioorganic and Medicinal Chemistry Letters. 2016 ; Vol. 26, No. 4. pp. 1333-1336.
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