title: Exploration of GGTase-I substrate requirements. Part 2: Synthesis and biochemical analysis of novel saturated geranylgeranyl diphosphate analogs.
abstract: Protein prenylation is a type of post-translational modification that aids certain proteins in localizing to the plasma member where they activate cell signaling. To better understand the isoprenoid requirements and differences of FTase and GGTase-I, a series of saturated geranylgeranyl diphosphate analogs were synthesized and screened against both mammalian FTase and GGTase-I. Of our library of compounds, several analogs proved to be substrates of GGTase-I, with 11d having a krel=0.95 when compared to GGPP (krel=1.0).
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA; The Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47909, USA. Electronic address: kayla.temple@vanderbilt.edu.
authors.forename: Kayla J
authors.initials: KJ
authors.lastname: Temple
authors.affiliation: Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Elia N
authors.initials: EN
authors.lastname: Wright
authors.affiliation: Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA; Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Fierke
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA; The Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47909, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D011106:Polyisoprenyl Phosphates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D011106:Polyisoprenyl Phosphates; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; C002963:geranylgeranyl pyrophosphate
keywords: Farnesylation; Geranylgeranylation; Isoprenoid synthesis; Protein prenylation; Saturated GGPP analogs