title: Stable propylphosphonic acid analogues of geranylgeranyl diphosphate possessing inhibitory activity on geranylgeranyl protein transferase.
abstract: Stable analogues of geranylgeranyl diphosphate, possessing 3-(phosphono)propionamido moieties in the place of the metabolically unstable diphosphate portion, were prepared and submitted to prenyltransferase (GGTase and FTase) inhibition assays. In one case, an excellent GGTase inhibitory activity was obtained (IC(50) = 39 nM), accompanied by a certain degree of GGTase vs. 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: Valentina
authors.initials: V
authors.lastname: Asso
authors.forename: Simone
authors.initials: S
authors.lastname: Bertini
authors.forename: Laura
authors.initials: L
authors.lastname: Betti
authors.forename: Gianbattista
authors.initials: G
authors.lastname: Gervasi
authors.forename: Elisa
authors.initials: E
authors.lastname: Ghilardi
authors.forename: Gino
authors.initials: G
authors.lastname: Giannaccini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Placanica
authors.forename: Giovanni
authors.initials: G
authors.lastname: Prota
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*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000494:pharmacology; D011106:Polyisoprenyl Phosphates / Q000138:chemical synthesis*
chemical_list: D004224:Diterpenes; D004791:Enzyme Inhibitors; D063065:Organophosphonates; D011106:Polyisoprenyl Phosphates; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; C064911:p21(ras) farnesyl-protein transferase; C002963:geranylgeranyl pyrophosphate