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Multiple Pathways for the Irreversible Inhibition of Steroid Sulfatase with Quinone Methide‐Generating Suicide Inhibitors
Author(s) -
Ahmed Vanessa,
Liu Yong,
Taylor Scott D.
Publication year - 2009
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200900143
Subject(s) - quinone methide , chemistry , sulfatase , steroid , steroid sulfatase , nucleophile , quinone , stereochemistry , biochemistry , enzyme , catalysis , hormone
Unexpected inhibition : 2‐ and 4‐mono‐ and difluoromethyl estrone sulfate derivatives are suicide inhibitors of steroid sulfatase (STS). Kinetic studies suggest that inhibition by the monofluoro derivatives is a result of a quinone methide intermediate that reacts with active‐site nucleophiles, whereas the main inhibition pathway of the 4‐difluoromethyl derivative is a result of decomposition of the initial quinone methide to an aldehyde that acts as potent, almost irreversible inhibitor.