Suicide inhibition

  (Redirected from Suicide inhibitor)

In biochemistry, suicide inhibition, also known as suicide inactivation or mechanism-based inhibition, is an irreversible form of enzyme inhibition that occurs when an enzyme binds a substrate analog and forms an irreversible complex with it through a covalent bond during the normal catalysis reaction. The inhibitor binds to the active site where it is modified by the enzyme to produce a reactive group that reacts irreversibly to form a stable inhibitor-enzyme complex. This usually uses a prosthetic group or a coenzyme, forming electrophilic alpha and beta unsaturated carbonyl compounds and imines.

Stereoisomers of Soman, a G-series nerve agent and suicide inhibitor of acetylcholinesterase. Note the non-carbon chiral center.


Some clinical examples of suicide inhibitors include:

Rational drug designEdit

Suicide inhibitors are used in what is called "rational drug design" where the aim is to create a novel substrate, based on already known mechanisms and substrates. The main goal of this approach is to create substrates that are unreactive until within that enzyme's active site and at the same time being highly specific. Drugs based on this approach have the advantage of very few resulting side effects.[3]

See alsoEdit


  1. ^ Aurbek N, Thiermann H, Szinicz L, Eyer P, Worek F (July 2006). "Analysis of inhibition, reactivation and aging kinetics of highly toxic organophosphorus compounds with human and pig acetylcholinesterase". Toxicology. 224 (1–2): 91–9. doi:10.1016/j.tox.2006.04.030. PMID 16720069.
  2. ^ Fowler JS (July 1977). "2-Methyl-3-butyn-2-ol as an acetylene precursor in the Mannich reaction. A new synthesis of suicide inactivators of monoamine oxidase". The Journal of Organic Chemistry. 42 (15): 2637–7. doi:10.1021/jo00435a026. PMID 874623.
  3. ^ Johnson DS, Weerapana E, Cravatt BF (June 2010). "Strategies for discovering and derisking covalent, irreversible enzyme inhibitors". Future Medicinal Chemistry. 2 (6): 949–64. doi:10.4155/fmc.10.21. PMC 2904065. PMID 20640225.