Stable propylphosphonic acid analogues of geranylgeranyl diphosphate possessing inhibitory activity on geranylgeranyl protein transferase.
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.
Minutolo
Filippo
F
Dipartimento di Scienze Farmaceutiche, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
Asso
Valentina
V
Bertini
Simone
S
Betti
Laura
L
Gervasi
Gianbattista
G
Ghilardi
Elisa
E
Giannaccini
Gino
G
Placanica
Giorgio
G
Prota
Giovanni
G
Rapposelli
Simona
S
Macchia
Marco
M
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*
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