Synthesis and activity of fluorescent isoprenoid pyrophosphate analogues.
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.
Kim
MeeKyoung
M
Department of Chemistry, University of Iowa, Iowa City, Iowa 52242-1294, USA.
Kleckley
Troy S
TS
Wiemer
Andrew J
AJ
Holstein
Sarah A
SA
Hohl
Raymond J
RJ
Wiemer
David F
DF
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
D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; C004808:farnesyl pyrophosphate; D018631:ras Proteins; C002963:geranylgeranyl pyrophosphate