DEVELOPMENT OF SURROGATE SUBSTRATES FOR NEUROPATHY TARGET ESTERASE

Seventeen substrates were synthesized and their activities as surrogat e substrates for Neuropathy Target Esterase were tested. Substrates in vestigated are carbon analogs of phenylvalerate, (1) with oxygen and s ulfur substituted at the alpha, beta and gamma positions. Phenol and t hiophenol esters of these analogs constitute two series of compounds t ested. The ratio of catalytic hydrolysis to background hydrolysis incr eased at lower pH values with all substrates tested including phenylva lerate (1). There was more than a 2.5-fold increase in specific activi ty with phenylthiopropylethanoate (6) at pH of 6.75 compared to phenyl valerate (1). Furthermore, a 19-fold decrease in K-m is reported with compound 6. This and related compounds can be used as the basis of mor e sensitive assays for neuropathy target esterase. Thiophenyl esters i n this series are sufficiently, good substrates to hold promise in con tinuous assays.