title: Synthesis and evaluation of 3- and 7-substituted geranylgeranyl pyrophosphate analogs.
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.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Maynor
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Scott
authors.forename: Emily L
authors.initials: EL
authors.lastname: Rickert
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure; D011106:Polyisoprenyl Phosphates / Q000138:chemical synthesis* / Q000494:pharmacology*; D017368:Protein Prenylation; D011499:Protein Processing, Post-Translational
chemical_list: D011106:Polyisoprenyl Phosphates; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D051231:Farnesyltranstransferase; C002963:geranylgeranyl pyrophosphate