Chapter 26. Recent Progress in the Design of Suicide Enzyme Inhibitors

摘要: Publisher Summary Because the enzyme becomes inactivated as a consequence of its own mechanism action, such inhibitors have been referred to “suicide inhibitors.” An inhibitor acting by would be expected extremely specific, because it should inactivate only those enzymes for which is substrate. A number α -difluoromethyl and α-monofluoromethylamino acids are potent irreversible corresponding amino acid decarboxylases. Aromatic decarboxylase, responsible conversion dopa dopamine, subject inactivation α-difluoromethyldopa α-monofluoromethyldopa. The former compound has selective peripheral action hence, increases central dopa, noradrenalin levels. cytochrome P-450 dependent enzyme, aromatase, catalyzes testosterone estradiol, propargylic alcohol. This was designed hydroxylated at C-19 in same manner normal NADPH 5-α-reductase reduction more androgen, dihydrotestosterone. It proposed that protonation step, implicit testosterone, activates diazoketone function then alkylates an active site nucleophile. Suicide inhibition is, course, not sole approach but considered complementary approaches based on transition state theory or judicial utilization binding sites.