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PLA 2 ‐mediated catalytic activation of its inhibitor 25‐acetyl‐petrosaspongiolide M: serendipitous identification of a new PLA 2 suicide inhibitor
Author(s) -
Monti M.C.,
Casapullo A.,
Riccio R.,
Gomez-Paloma L.
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.10.100
Subject(s) - covalent bond , chemistry , enzyme inhibitor , enzyme , catalysis , stereochemistry , active site , combinatorial chemistry , biochemistry , organic chemistry
25‐Acetyl‐petrosaspongiolide M (PMAc) (1), a mild non‐covalent PLA 2 inhibitor, unexpectedly recovers, after incubation with bv PLA 2 , the ability to covalently modify the enzyme target. This study demonstrates the catalytic effect of bv PLA 2 in converting 1 in its deacetylated congener petrosaspongiolide M (PM) (2), a strong covalent PLA 2 inhibitor whose molecular mechanism of inhibition has already been clarified. Moreover, our findings outline the potential role of PMAc as anti‐inflammatory pro‐drug, by virtue of its ability of delivering the active PM agent at the site of inflammation, functioning as a suicide inhibitor.