Trojan horse inactivators

The efficiency of inactivation by covalent bond formation vs release of the reactive species into solution has been described by its partition ratio. The most efficient inactivators have catalytic partition ratios of 0, in which case each inhibitor molecule leads to inactivation of the enzyme. To this date, many of these inhibitors have been designed, and alternative names like suicide substrate, Trojan Horse inactivator, enzyme induced inactivator, inhibitor, and latent inactivator have been used for this class of inhibitors. A number of comprehensive reviews are available (26—32). 

Suicide Substrates. Much like affinity labels, suicide inhibitors first form a reversible complex with the target enzyme due to the structural similarity between inhibitor and substrate. In a subsequent time dependent step, an irreversible complex (usually covalent) is formed with an appropriately positioned amino acid side chain. Unlike the affinity label, suicide substrates (65) are not inherently reactive and must undergo activation by the target enzyme before the irreversible complex is formed. Therefore, these inhibitors are generally more selective than affinity labels. Since the enzyine catalyzes its own inactivation, these inhibitors are also known as kcat inhibitors (66), enzyme-activated, irreversible inhibitors (54) and Trojan horse reagents (6. ... 

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