Synthesis and evaluation of 3- and 7-substituted geranylgeranyl pyrophosphate analogs.
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.
Maynor
Michelle
M
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Purdue University, West Lafayette, IN 47907, USA.
Scott
Sarah A
SA
Rickert
Emily L
EL
Gibbs
Richard A
RA
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
D011106:Polyisoprenyl Phosphates; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D051231:Farnesyltranstransferase; C002963:geranylgeranyl pyrophosphate