REACTIVITY AND STEREOSPECIFICITY OF NEUROPATHY TARGET ESTERASE AND ALPHA-CHYMOTRYPSIN WITH 2-SUBSTITUTED-4H-1,3,2-BENZODIOXAPHOSPHORIN 2-OXIDES

2-Substituted-4H-1,3,2-benzodioxaphosphorin 2-oxides (2-substituted-BD POs) a re of special interest as neuropathy target esterase (NTE) inhi bitors because they include not only the neuropathic metabolite of tri -o-cresyl phosphate (the 2-methylphenoxy analog) but also the most pot ent NTE inhibitors known. These compounds react much faster with NTE t han 2 standard inhibitors, O,O-diisopropyl fluorophosphonate (DFP) and mipafox. alpha-Chymotrypsin is similar to NTE in undergoing rapid inh ibition by BDPOs which is known to involve phosphorylation followed by aging. NTE and alpha-chymotrypsin were compared for reaction rates wi th BDPOs varying in the 2-substituent as follows: 4-methyl-, 4-propyl- , and 4-hexylphenoxy; butyl, octyl and dodecyl; (S)- and (R)-butyl. Th e active site of NTE differs from that of alpha-chymotrypsin in prefer ence for long-chain substituents and in stereospecificity.