Stable analogues of geranylgeranyl diphosphate possessing improved geranylgeranyl versus farnesyl protein transferase inhibitory selectivity.
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.
Minutolo
Filippo
F
Dipartimento di Scienze Farmaceutiche, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
Bertini
Simone
S
Betti
Laura
L
Danesi
Romano
R
Gervasi
Gianbattista
G
Giannaccini
Gino
G
Papi
Chiara
C
Placanica
Giorgio
G
Barontini
Silvia
S
Rapposelli
Simona
S
Macchia
Marco
M
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
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