期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 9, 期 2, 页码 237-243出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0968-0896(00)00239-X
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N-(2-Chloroethyl)-N-methylphenylalanine was designed and synthesized in an optically active form as a novel class of mechanism-based inactivator for carboxypeptidase A (CPA). It was anticipated that the chloroethylamino moiety of the CPA bound inhibitor undergoes an intramolecular S(N)2 reaction to generate a chemically reactive species (an aziridinium ion) which is expectedly subjected to a nucleophilic attack by the carboxylate of Glu-270, leading to covalent modification of the carboxylate. The irreversible nature of the inhibition of CPA by the inhibitor was supported by the kinetic data: the enzyme lost its enzymic activity in a time-dependent manner in the presence of the inhibitor and the inactivated CPA failed to regain the activity upon dialysis. Interestingly, the (R)-isomer that belongs to the D-series was more potent than its enantiomer. (C) 2001 Elsevier Science Ltd. All rights reserved.
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