Synthesis and activity of fluorescent isoprenoid pyrophosphate analogues

Mee Kyoung Kim, Troy S. Kleckley, Andrew J. Wiemer, Sarah A. Holstein, Raymond Hohl, David F. Wiemer

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)8186-8193
Number of pages8
JournalJournal of Organic Chemistry
Volume69
Issue number24
DOIs
StatePublished - Nov 26 2004

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Diphosphates
Terpenes
Farnesol
Alcohols
Metabolism
Amines
Culture Media
Assays
Fluorescence
Cells
Enzymes
diphosphoric acid
farnesyl pyrophosphate
geranylgeraniol

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Cite this

Kim, M. K., Kleckley, T. S., Wiemer, A. J., Holstein, S. A., Hohl, R., & Wiemer, D. F. (2004). Synthesis and activity of fluorescent isoprenoid pyrophosphate analogues. Journal of Organic Chemistry, 69(24), 8186-8193. https://doi.org/10.1021/jo049101w
Kim, Mee Kyoung ; Kleckley, Troy S. ; Wiemer, Andrew J. ; Holstein, Sarah A. ; Hohl, Raymond ; Wiemer, David F. / Synthesis and activity of fluorescent isoprenoid pyrophosphate analogues. In: Journal of Organic Chemistry. 2004 ; Vol. 69, No. 24. pp. 8186-8193.
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Kim, MK, Kleckley, TS, Wiemer, AJ, Holstein, SA, Hohl, R & Wiemer, DF 2004, 'Synthesis and activity of fluorescent isoprenoid pyrophosphate analogues', Journal of Organic Chemistry, vol. 69, no. 24, pp. 8186-8193. https://doi.org/10.1021/jo049101w

Synthesis and activity of fluorescent isoprenoid pyrophosphate analogues. / Kim, Mee Kyoung; Kleckley, Troy S.; Wiemer, Andrew J.; Holstein, Sarah A.; Hohl, Raymond; Wiemer, David F.

In: Journal of Organic Chemistry, Vol. 69, No. 24, 26.11.2004, p. 8186-8193.

Research output: Contribution to journalArticle

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AU - Kim, Mee Kyoung

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AU - Wiemer, David F.

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AB - 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.

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