PLA 2-mediated catalytic activation of its inhibitor 25-acetyl-petrosaspongiolide M: serendipitous identification of a new PLA 2 suicide inhibitor

• Published in: FEBS letters Vol. 578; no. 3; pp. 269 - 274
• Main Authors: Monti, M.C., Casapullo, A., Riccio, R., Gomez-Paloma, L.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 17-12-2004
• Subjects: Anti-inflammatory compound; Marine natural product; Mass spectrometry; Phospholipase A 2 inhibition; RP-HPLC; CD; DOPG; SUV’s; Marine natural product; Phospholipase A 2 inhibition; ESI-MS; bvPLA 2; Anti-inflammatory compound; PLA 2; Mass spectrometry; TFA
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2004.10.100

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.