title: Phosphonomethylphosphorylmethyl(oxy)-analogues of geranylgeranyl diphosphate as stable and selective geranylgeranyl protein transferase inhibitors.
abstract: The diphosphate moiety of geranylgeranyldiphosphate (GGdP) was replaced with metabolically and hydrolytically stable analogous polar portions, in an attempt to obtain new geranylgeranyltransferase (GGTase) inhibitors, which could also be selective over congener enzyme farnesyltransferase (FTase). In particular, the phosphonomethylphosphorylmethoxy derivative showed the highest inhibition potency, accompanied by a satisfactory GGTase/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: Michela
authors.initials: M
authors.lastname: Antonello
authors.forename: Silvia
authors.initials: S
authors.lastname: Barontini
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: 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 / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D011106:Polyisoprenyl Phosphates / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D004224:Diterpenes; D004791:Enzyme Inhibitors; D009943:Organophosphorus Compounds; D011106:Polyisoprenyl Phosphates; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; C002963:geranylgeranyl pyrophosphate