Synthesis and evaluation of 3- and 7-substituted geranylgeranyl pyrophosphate analogs

doi:10.1016/j.bmcl.2008.02.014

Bioorganic & Medicinal Chemistry Letters

Volume 18, Issue 6, 15 March 2008, Pages 1889-1892

https://doi.org/10.1016/j.bmcl.2008.02.014 Get rights and content

Abstract

Protein prenyl transferases have been a focus of anti-cancer drug discovery in recent years due to their roles in post-translational modification of small GTP binding proteins. Attention is now turning to the development of GGTase I inhibitors. Here, we present the synthesis and biological evaluation of four GGPP analogs versus mammalian GGTase I and the discovery that 7-allyl GGPP is a surprisingly efficient GGTase I substrate.

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Acknowledgments

This work was supported by NIH Grants CA78819 and P30CA21368 (Purdue Cancer Center). E.L.R. was supported by a US Army Breast Cancer Summer Undergraduate Research Program. We thank Professor Carol Fierke (Department of Chemistry, University of Michigan) for supplying us with GGTase I.

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Synthesis and evaluation of 3- and 7-substituted geranylgeranyl pyrophosphate analogs

Abstract

Graphical abstract

Section snippets

Acknowledgments

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J. Lipid Res.

J. Biol. Chem.

J. Biol. Chem.

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Bioorg. Med. Chem. Lett.

Trends Pharmacol. Sci.

Biochem. Biophys. Res. Commun.

Bioorg. Med. Chem. Lett.

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