The mechanism of the irreversible inhibition of estrone sulfatase (ES) through the consideration of a range of methane- and amino-sulfonate-based compounds.
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.
Ahmed
Sabbir
S
School of Chemical and Pharmaceutical Sciences, Kingston University, Penrhyn Road, Surrey, KT1 2EE, Kingston upon Thames, UK. ch_s534@kingston.ac.uk
James
Karen
K
Owen
Caroline P
CP
Patel
Chirag K
CK
Sampson
Luther
L
D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008697:Methane / Q000737:chemistry*; D013429:Sulfatases / Q000037:antagonists & inhibitors*; D013451:Sulfonic Acids / Q000737:chemistry*
D004791:Enzyme Inhibitors; D013451:Sulfonic Acids; C005741:sulfamic acid; D013429:Sulfatases; C020121:estrone sulfatase; D008697:Methane