title: Stable analogues of geranylgeranyl diphosphate possessing improved geranylgeranyl versus farnesyl protein transferase inhibitory selectivity.
abstract: Phosphonoacetamido(oxy) groups have proven to be good mimics of the diphosphate portion in geranylgeranyl protein transferase I (GGTase I) inhibitors. The introduction of small alkyl groups (Me, Et) into the diphosphate mimic moiety caused a further decrease in collateral farnesyl protein transferase (FTase) inhibitory activity, thereby improving GGTase I over FTase selectivity.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Minutolo
authors.forename: Simone
authors.initials: S
authors.lastname: Bertini
authors.forename: Laura
authors.initials: L
authors.lastname: Betti
authors.forename: Romano
authors.initials: R
authors.lastname: Danesi
authors.forename: Gianbattista
authors.initials: G
authors.lastname: Gervasi
authors.forename: Gino
authors.initials: G
authors.lastname: Giannaccini
authors.forename: Chiara
authors.initials: C
authors.lastname: Papi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Placanica
authors.forename: Silvia
authors.initials: S
authors.lastname: Barontini
authors.forename: Simona
authors.initials: S
authors.lastname: Rapposelli
authors.forename: Marco
authors.initials: M
authors.lastname: Macchia
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D004224:Diterpenes; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D011106:Polyisoprenyl Phosphates / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D004224:Diterpenes; D004791:Enzyme Inhibitors; D011106:Polyisoprenyl Phosphates; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; C064911:p21(ras) farnesyl-protein transferase; C002963:geranylgeranyl pyrophosphate