Synthesis and activity of fluorescent isoprenoid pyrophosphate analogues

J Org Chem. 2004 Nov 26;69(24):8186-93. doi: 10.1021/jo049101w.

Abstract

New fluorescent analogues of farnesol and geranylgeraniol have been prepared and then converted to the corresponding pyrophosphates. These analogues incorporate anthranylate or dansyl-like groups anchored to the terpenoid skeleton through amine bonds that would be expected to be relatively stable to metabolism. After addition of the alcohols or the pyrophosphates to the culture medium, their fluorescence is readily observed inside a human-derived leukemia cell line. Enzyme assays have revealed that the farnesyl pyrophosphate analogue is an inhibitor of FTase, while the corresponding alcohol is not. These results, together with Western blot analyses of cell lysates, indicate that the farnesyl pyrophosphate analogue penetrates the cells as an intact pyrophosphate and that it does so at a biologically relevant concentration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cells, Cultured
  • Fluorescence*
  • Humans
  • Molecular Structure
  • Polyisoprenyl Phosphates / chemical synthesis*
  • Polyisoprenyl Phosphates / chemistry
  • Polyisoprenyl Phosphates / pharmacokinetics*
  • Protein Prenylation / drug effects
  • Sesquiterpenes
  • ras Proteins / drug effects
  • ras Proteins / metabolism

Substances

  • Polyisoprenyl Phosphates
  • Sesquiterpenes
  • farnesyl pyrophosphate
  • ras Proteins
  • geranylgeranyl pyrophosphate