Stereoselective inhibition of human butyrylcholinesterase by phosphonothiolate analogs of (+)- and (-)-cocaine.
Stereoselective inhibition of human butyrylcholinesterase by phosphonothiolate analogs of (+)- and (-)-cocaine.
复制标题
()-和(-)-可卡因的硫代膦酸类似物立体选择性抑制人丁酰胆碱酯酶。
DOI：
10.1016/s0006-2952(97)00403-6
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发表时间：
1997
影响因子：
5.8
通讯作者：
Cashman,JR
中科院分区：
文献类型：
--
作者：
Berkman,CE;Underiner,GE;Cashman,JR
The hydrolysis of cocaine (benzoylecgonine methyl ester) to ecgonine methyl ester by human butyrylcholinesterase (BuChE; EC 3.1.1.8) has been shown previously to constitute an important means to detoxicate this material to pharmacologically inactive metabolites. The naturally occurring (−)-cocaine is hydrolyzed to ecgonine methyl ester approximately 2000 times slower than the unnatural (+)-cocaine isomer. In good agreement with previous studies, (−)-cocaine bound to human BuChE with relatively good affinity and competitively inhibited the hydrolysis of the spectrophotometric substrate butyrylthiocholine with a Kivalue of 8.0 μM. Similarly, (+)-cocaine also showed relatively high affinity for the human BuChE and competitively inhibited butyrylthiocholine hydrolysis with a Kivalue of 5.4 μM. The phosphonothiolates corresponding to the transition state analogs for both (−)- and (+)-cocaine hydrolysis were synthesized and tested as inhibitors of human BuChE-catalyzed hydrolysis of butyrylthiocholine. The phosphonothiolate corresponding to the transition state for (−)-cocaine hydrolysis was a competitive inhibitor with a Kivalue of 55.8 μM. The phosphonothiolate corresponding to the transition state for (+)-cocaine hydrolysis gave a Kivalue of 25.9 μM, but, in addition, it also showed irreversible inhibition with a kiof inactivation of 68.8 min−1M−1. It is likely that the mechanism-based inhibitor described herein may find use as a mechanistic probe of butyrylcholinesterase action and also possibly aid in the purification of this class of esterases.
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影响因子：
5.3
作者：
E. Rahdert;D. Czechowicz
通讯作者：
D. Czechowicz
影响因子：
56.9
作者：
KOOB, GF;BLOOM, FE
通讯作者：
BLOOM, FE
DOI：
10.16480/j.cnki.cn43-1326/c.2026.02.013
发表时间：
2026-03-01
期刊：
湖南干部教育培训研究
影响因子：
--
作者：
邓玲丽
通讯作者：
--
影响因子：
21.1
作者：
C. Johanson;M. Fischman
通讯作者：
C. Johanson;M. Fischman
影响因子：
4.1
作者：
BERKMAN, CE;QUINN, DA;THOMPSON, CM
通讯作者：
THOMPSON, CM