Serine proteinases irreversible inhibitors

A potent irreversible inhibitor (abbreviated DFP) of many serine proteinases and serine esterases (especially acetylcholinesterase). This substance is EXTREMELY POISONOUS, but the vapor state can be minimized by using dry, water-miscible solvents such as 2-propanoL. Aqueous solutions become inactivated by hydrolysis, but solutions made with dry 2-propanol are stable at -20°C for many months. 

SERINE DEHYDRATASE SERINE DEHYDRATASE SERINE DEHYDROGENASE Serine esterase inhibitor, irreversible, PHENYLMETHYLSULFONYL FLUORIDE SERINE HYDROXYMETHYLTRANSFERASE SERINE PALMITOYLTRANSFERASE Serine protease inhibitor, irreversible, PHENYLMETHYLSULFONYL FLUORIDE Serine proteinase inhibitor,... 

Peptidic monohalomethyl ketones inactivate serine proteinases by irreversibly reacting with the active-site histidine [101]. However, because of the reactivity pattern and the mechanism of action shown by these compounds, they are described in this section. Although initially prepared as inhibitors of other proteinases, monohalomethyl ketones contributed to the studies on elastase-ligand interactions. They supplied key data points on (a) the effect of the peptide substrate length on the binding, and (b) the subsite specificity of PPE and HLE. Kinetic evaluation of these compounds indicated a two-step mechanism for enzymatic inhibition (Equation 2.2). 

Irreversible inhibition can also occur in the presence of halogenated methyl ketones which alkylate the active histidine residue (cf. 2.4.1.1), or as a result of the action of proteinase inhibitors, which are also proteins, by interaction with the enzyme to form inactive complexes. These natural inhibitors are found in the organs of animals and plants (pancreas, colostrum, egg white, potato tuber and seeds of many legumes cf. 16.2.3). The specificity of serine... 

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