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Probing the Activities and Mechanisms of Leukotriene A 4 Hydrolase with Synthetic Inhibitors
Author(s) -
Hogg J. Heather,
Ollmann Ian R.,
Wetterholm Anders,
Blomster Andberg Martina,
Haeggström Jesper,
Samuelsson Bengt,
Wong ChiHuey
Publication year - 1998
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/(sici)1521-3765(19980904)4:9<1698::aid-chem1698>3.0.co;2-j
Subject(s) - epoxide hydrolase , hydrolase , epoxide hydrolase 2 , chemistry , active site , mutagenesis , stereochemistry , biochemistry , enzyme , leukotriene , biology , mutation , immunology , gene , microsome , asthma
The synthesis of a potent competitive LTA 4 hydrolase inhibitor ( A , K i =1.6 n M ) prompted an investigation into the biological activity of A against LTB 4 biosynthesis, as well as the design, synthesis, and evaluation of a new series of inhibitors B to further probe the active site of LTA 4 hydrolase. On the basis of these results, and previously reported site‐directed mutagenesis and inhibition studies, the mechanisms of peptide and epoxide hydrolysis catalyzed by LTA 4 hydrolase are discussed.