Linderman_1988_Pestic.Biochem.Physiol_31_187

Fluoroketones have been developed as highly potent, specific inhibitors of insect juvenile hormone esterase. These compounds are believed to function as transition state analog inhibitors of the enzyme. Of the fluoroketones prepared, 3-octylthio-1,1,1-trifluoropropan-2-one has been extensively studied, yet no analysis of the actual mode of enzyme inhibition has been reported. A 19F-NMR analysis of the inhibition of a hydrolytic enzyme, acetylcholinesterase, by 3-octylthio-1,1,1-trifluoropropan-2-one was carried out. Experiments with phosphorylated acetyl-cholinesterase determined that interaction of the fluoroketone with the enzyme is specific for the esteratic active site serine residue. The carbonyl moiety of the fluoroketone is required for binding and inhibition. The fluoroketone binds to the enzyme active site in a tetrahedral form, indicating that 3-octylthio-1,1,1-trifluoropropan-2-one does function as a transition state analog inhibitor of a hydrolytic enzyme.