Antiflammin-2 (HDMNKVLDL) does not inhibit phospholipase A2 activities.
A basic nonapeptide P2 (antiflammin-2, HDMNKVLDL) which is identical to a portion of the amino acid sequence (residues 246-254) of lipocortin I, has been described to have antiinflammatory activity in a rat paw edema model (Nature 335: 726-730 [1988]). P2 (0.05 microM) was also reported to inhibit porcine pancreatic phospholipase A2 (PLA2). The effect of synthetic P2 (98% pure) on PLA2 was evaluated in two assay systems. Using porcine pancreatic PLA2 and phosphatidylcholine/deoxycholate mixed micellar substrate, P2 (0.005-50 microM) had no effect on PLA2 activity, even in the presence of 2-mercaptoethanol to prevent peptide oxidation. In another assay, using human synovial fluid PLA2 as the enzyme and [14C]-oleate-labelled E. coli substrate, P2 (0.005-50 microM) had no significant effect on PLA2 activity. A reported PLA2 inhibitor, manoalide, was a potent inhibitor of PLA2 in both assay systems. On the basis of these results, we conclude that P2 is devoid of PLA2 inhibitory activity.
Hope
W C
WC
Department of Allergy and Inflammation Research, Hoffmann-La Roche Inc., Nutley, NJ 07110.
Patel
B J
BJ
Bolin
D R
DR
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D010179:Pancreas / Q000201:enzymology; D010446:Peptide Fragments / Q000494:pharmacology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D013552:Swine; D013582:Synovial Fluid / Q000201:enzymology; D013729:Terpenes / Q000494:pharmacology
D009842:Oligopeptides; D010446:Peptide Fragments; D013729:Terpenes; C064647:antiflammin P2; C045673:manoalide; D010741:Phospholipases A; D054467:Phospholipases A2