Evidence for the mechanism of the irreversible inhibition of oestrone sulphatase (ES) by aminosulphonate based compounds

Ahmed, Sabbir, Owen, Caroline P., James, Karen, Patel, Chirag K. and Sampson, Luther (2002) Evidence for the mechanism of the irreversible inhibition of oestrone sulphatase (ES) by aminosulphonate based compounds. The Journal of Steroid Biochemistry and Molecular Biology, 80(4-5), pp. 429-440. ISSN (print) 0960-0760

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Abstract

In our search for the mechanism of the enzyme oestrone sulphatase (ES) we have synthesised and evaluated a number of compounds that were predicted to possess some inhibitory activity. Some of these compounds were indeed found to be inhibitors of ES, whilst other compounds were not. From a consideration of the structure-activity relationship (SAR) of the inhibitors and non-inhibitors of this enzyme, we discovered a factor which we now believe is the main inhibitory moiety within the aminosulphonated inhibitors. We therefore report the results of our study into a series of phenyl and alkyl sulphamated compounds as inhibitors of ES. The results of the study show that the substituted phenyl sulphamates are potent inhibitors, whereas the alkyl compounds are, in general, non-inhibitors. Using the results of our SAR study, we postulate the probable mechanism for the irreversible and reversible inhibition of ES, and rationalise the role of the different physicochemical factors in the inhibition of this crucial enzyme.

Item Type: Article
Uncontrolled Keywords: oestrone, sulphatase, mechanism, inhibitors, aminosulphamate, site-directed inhibitor, estrone sulfatase, active-site, steroid sulfatase, potent inhibitors, substrate
Research Area: Chemistry
Faculty, School or Research Centre: Faculty of Science (until 2011) > School of Pharmacy and Chemistry
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Depositing User: David Salliss
Date Deposited: 19 Jun 2007
Last Modified: 18 Mar 2011 11:00
URI: http://eprints.kingston.ac.uk/id/eprint/1383

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