Evaluation of geranylazide and farnesylazide diphosphate for incorporation of prenylazides into a CAAX box-containing peptide using protein farnesyltransferase

M. W. Rose, N. D. Rose, J. Boggs, S. Lenevich, J. Xu, G. Barany, M. D. Distefano

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Protein farnesyltransferase (PFTase) catalyzes the attachment of a geranylazide (C10) or farnesylazide (C15) moiety from the corresponding prenyldiphosphates to a model peptide substrate, N-dansyl-Gly-Cys-Val-Ile-Ala- OH. The rates of incorporation for these two substrate analogs are comparable and approximately twofold lower than that using the natural substrate farnesyl diphosphate (FPP). Reaction of N-dansyl-Gly-Cys (S-farnesylazide)-Val-Ile-Ala-OH with 2-diphenylphosphanylbenzoic acid methyl ester then gives a stable alkoxy-imidate linked product. This result suggests future generations whereby azide groups introduced using this enzymatic approach are functionalized using a broad range of azide-reactive reagents. Thus, chemistry has been developed that could be used to achieve highly specific peptide and protein modification. The farnesylazide analog may be useful in certain biological studies, whereas the geranylazide group may be more useful for general protein modification and immobilization. Copyright Blackwell Munksgaard, 2005.

Original languageEnglish (US)
Pages (from-to)529-537
Number of pages9
JournalJournal of Peptide Research
Volume65
Issue number6
DOIs
StatePublished - Jun 1 2005

Keywords

  • CAAX box
  • Cysteine modification
  • Farnesylazide
  • Farnesyltransferase
  • Geranylazide
  • Peptide modification
  • Prenylated peptides
  • Prenylazide

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