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

• Published in: Bioorganic & medicinal chemistry Vol. 18; no. 6; pp. 1889 - 1892
• Main Authors: Maynor, Michelle, Scott, Sarah A., Rickert, Emily L., Gibbs, Richard A.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.03.2008; Elsevier
• Subjects: Alkyl and Aryl Transferases - antagonists & inhibitors; Animals; Biological and medical sciences; Farnesyltranstransferase - antagonists & inhibitors; Geranylgeranylation; Humans; Isoprenoids; Magnetic Resonance Spectroscopy; Medical sciences; Mice; Miscellaneous; Molecular Structure; Palladium-catalyzed coupling; Pharmacology. Drug treatments; Polyisoprenyl Phosphates - chemical synthesis; Polyisoprenyl Phosphates - pharmacology; Post-translational modification; Protein Prenylation; Protein Processing, Post-Translational; Post-translational modification; Palladium-catalyzed coupling; Geranylgeranylation; Isoprenoids; Catalytic reaction; Enzyme; Palladium Complexes; Transferases; Isoprenoid; Biological activity; Posttranslational modification; Substrate; Organic diphosphate; Platinoid Complexes; Inhibitor; Chemical synthesis
• ISSN: 0960-894X; 0968-0896; 1464-3405; 1464-3405; 1464-3391
• DOI: 10.1016/j.bmcl.2008.02.014

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.