The mechanism of the irreversible inhibition of estrone sulfatase (ES) through the consideration of a range of methane- and amino-sulfonate-based compounds

Ahmed, Sabbir, James, Karen, Owen, Caroline P., Patel, Chirag K. and Sampson, Luther (2002) The mechanism of the irreversible inhibition of estrone sulfatase (ES) through the consideration of a range of methane- and amino-sulfonate-based compounds. Bioorganic & Medicinal Chemistry Letters, 12(9), pp. 1279-1282. ISSN (print) 0960-894X

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Abstract

We report the results of our study into a series of simple phenyl and alkyl sulfamates and alkyl methanesulfonates as potential inhibitors of the enzyme estrone sulfatase (ES). The results of the study show that the substituted phenyl sulfamates are good irreversible inhibitors; the alkyl sulfamate compounds were found to lack inhibitory activity; whilst the large alkyl chain containing methanesulfonate-based compounds were found to possess weak reversible inhibitory activity. Using the results of the inhibition study, we postulate the probable mechanism for ES and suggest that an attack by the gem-diol is a major requirement prior to the hydrolysis of the sulfamate group, following which, attack on the active site C=O occurs and which therefore leads to the production of an imine type functionality, resulting in irreversible inhibition.

Item Type: Article
Uncontrolled Keywords: steroid sulfatase
Research Area: Chemistry
Faculty, School or Research Centre: Faculty of Science (until 2011) > School of Pharmacy and Chemistry
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Depositing User: Automatic Import Agent
Date Deposited: 11 Mar 2010 08:18
Last Modified: 14 Apr 2011 12:11
URI: http://eprints.kingston.ac.uk/id/eprint/7205

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