25-Acetyl-petrosaspongiolide M (PMAc) (1), a mild non-covalent PLA(2) inhibitor, unexpectedly recovers, after incubation with bvPLA(2), the ability to covalently modify the enzyme target. This study demonstrates the catalytic effect of bvPLA(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.

PLA2-mediated catalytic activation of its inhibitor 25-acetyl-petrosaspongiolide M: serendipitous identification of a new PLA2 suicide inhibitor / Monti, Maria Chiara; Casapullo, Agostino; Riccio, Raffaele; GOMEZ PALOMA, L.. - In: FEBS LETTERS. - ISSN 0014-5793. - 578:(2004), pp. 269-274. [10.1016/j.febslet.2004.10.100]

PLA2-mediated catalytic activation of its inhibitor 25-acetyl-petrosaspongiolide M: serendipitous identification of a new PLA2 suicide inhibitor

MONTI, Maria Chiara;CASAPULLO, Agostino;RICCIO, Raffaele;
2004

Abstract

25-Acetyl-petrosaspongiolide M (PMAc) (1), a mild non-covalent PLA(2) inhibitor, unexpectedly recovers, after incubation with bvPLA(2), the ability to covalently modify the enzyme target. This study demonstrates the catalytic effect of bvPLA(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.
2004
PLA2-mediated catalytic activation of its inhibitor 25-acetyl-petrosaspongiolide M: serendipitous identification of a new PLA2 suicide inhibitor / Monti, Maria Chiara; Casapullo, Agostino; Riccio, Raffaele; GOMEZ PALOMA, L.. - In: FEBS LETTERS. - ISSN 0014-5793. - 578:(2004), pp. 269-274. [10.1016/j.febslet.2004.10.100]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/951350
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