title: Synthesis and activity of fluorescent isoprenoid pyrophosphate analogues.
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.
authors.affiliation: Department of Chemistry, University of Iowa, Iowa City, Iowa 52242-1294, USA.
authors.forename: MeeKyoung
authors.initials: M
authors.lastname: Kim
authors.forename: Troy S
authors.initials: TS
authors.lastname: Kleckley
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wiemer
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Holstein
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Hohl
authors.forename: David F
authors.initials: DF
authors.lastname: Wiemer
mesh_terms: D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005453:Fluorescence; D006801:Humans; D015394:Molecular Structure; D011106:Polyisoprenyl Phosphates / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D017368:Protein Prenylation / Q000187:drug effects; D012717:Sesquiterpenes; D018631:ras Proteins / Q000187:drug effects / Q000378:metabolism
chemical_list: D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; C004808:farnesyl pyrophosphate; D018631:ras Proteins; C002963:geranylgeranyl pyrophosphate