Pefabloc, 4-[2-aminoethyl]benzenesulfonyl fluoride, is a new, potent nontoxic and irreversible inhibitor of PAF-degrading acetylhydrolase.
We report here that 4-[2-aminoethyl]benzenesulfonyl fluoride (Pefabloc SC, Pefabloc), a new irreversible serine proteinase inhibitor, efficiently inhibits both human and rat platelet activating factor (PAF)-degrading acetylhydrolase (acetylhydrolase). Indeed, low concentrations of Pefabloc (0.1 mM) rapidly and totally inactivate both human plasma-, VLDL-, IDL-, LDL- and HDL-associated acetylhydrolase, and in addition, acetylhydrolase synthesized and released by human adherent monocytes in culture, as well as rat brain cytosolic acetylhydrolase. By contrast, Pefabloc only minimally inhibited the phospholipase A2 (PLA2) activity from Naja naja and from porcine pancreas. In addition, Pefabloc is relatively nontoxic, stable and convenient to use. Henceforth, Pefabloc may replace both DFP and PMSF and therefore constitutes a useful and valuable tool in future studies of acetylhydrolase.
Dentan
C
C
Institut National de la Santé et de la Recherche (INSERM), Unité de Recherches sur les Lipoprotéines et l'Athérogénèse, Hôpital de la Pitié, Paris, France.
Tselepis
A D
AD
Chapman
M J
MJ
Ninio
E
E
D015060:1,2-Dipalmitoylphosphatidylcholine; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D001921:Brain / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004798:Enzymes / Q000096:biosynthesis; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D009000:Monocytes / Q000201:enzymology; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000378:metabolism; D051381:Rats; D013450:Sulfones / Q000494:pharmacology*; D014361:Trypsin Inhibitors / Q000494:pharmacology*
D004798:Enzymes; D008074:Lipoproteins; D010972:Platelet Activating Factor; D013450:Sulfones; D014361:Trypsin Inhibitors; D015060:1,2-Dipalmitoylphosphatidylcholine; C002010:4-(2-aminoethyl)benzenesulfonylfluoride; D010664:Phenylmethylsulfonyl Fluoride; D010741:Phospholipases A; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase