A. Dafforn, J. Neenan, C. Ash
Jan 29, 1982
Citations
0
Influential Citations
6
Citations
Journal
Biochemical and biophysical research communications
Abstract
Abstract 1-Phenoxy-2-propanone, 1-chloro-3-phenoxy-2-propanone, and 1-fluoro-3-phenoxy-2-propanone are competitive acetylcholinesterase inhibitors with K I values of 30, 0.85, and 2.2 μM, respectively, compared to 2 mM for 4-phenyl-2-butanone. The substituent effect on inhibition suggests that these compounds bind by formation of a tetrahedral adduct and are transition state analogs. Other evidence supports this conclusion: N-benzyl-2-chloroacetamide and 1-phenoxy-2-propanol are poor inhibitors (K I = 11 and >10 mM); 1-phenoxy-2-propanone and 1-chloro-3-phenoxy-2-propanone have K I values 330 and 140 times smaller than K m for corresponding substrates; and 1-chloro-3-phenoxy-2-propanone protects the enzyme against irreversible inhibition by CH 3 SO 2 F.