Effect of synthetic and natural phospholipids on N-acylphosphatidylethanolamine-hydrolyzing phospholipase D activity
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Effect of synthetic and natural phospholipids on N-acylphosphatidylethanolamine-hydrolyzing phospholipase D activity. / Petersen, Gitte; Pedersen, Anders H; Pickering, Darryl S; Begtrup, Mikael; Hansen, Harald S.
In: Chemistry and Physics of Lipids, Vol. 162, No. 1-2, 2009, p. 53-61.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Effect of synthetic and natural phospholipids on N-acylphosphatidylethanolamine-hydrolyzing phospholipase D activity
AU - Petersen, Gitte
AU - Pedersen, Anders H
AU - Pickering, Darryl S
AU - Begtrup, Mikael
AU - Hansen, Harald S
PY - 2009
Y1 - 2009
N2 - N-Acylethanolamines (NAEs) constitute a family of endogenous bioactive lipids that includes arachidonoylethanolamide (anandamide), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). These lipids are formed from their respective N-acylated ethanolamine phospholipid (NAPE) precursor by the action of a phospholipase D enzyme (NAPE-PLD). Anandamide, OEA, and PEA are all bioactive lipids that may influence, amongst others: neuroinflammation, food intake, and oocyte implantation. Here we have synthesized a number of NAPE analogues with variation in the phosphoester structure. The NAPE analogues as well as selected phospholipids and beta-lactamase substrates were tested as potential modifiers of cloned human NAPE-PLD in an enzyme assay involving a (14)C-labeled diether-NAPE substrate. One hit was identified, namely 1,2-dihexanoyl-glycero-N-(3-(tetradecanoylamino)propyl)phosphoramidate (AHP-71B) which showed inhibitory activity and may serve as template for further structure-activity developments. Furthermore, it was found that NAPE-PLD was activated by phosphatidylethanolamine and inhibited by the beta-lactamase substrate nitrocefin.
AB - N-Acylethanolamines (NAEs) constitute a family of endogenous bioactive lipids that includes arachidonoylethanolamide (anandamide), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). These lipids are formed from their respective N-acylated ethanolamine phospholipid (NAPE) precursor by the action of a phospholipase D enzyme (NAPE-PLD). Anandamide, OEA, and PEA are all bioactive lipids that may influence, amongst others: neuroinflammation, food intake, and oocyte implantation. Here we have synthesized a number of NAPE analogues with variation in the phosphoester structure. The NAPE analogues as well as selected phospholipids and beta-lactamase substrates were tested as potential modifiers of cloned human NAPE-PLD in an enzyme assay involving a (14)C-labeled diether-NAPE substrate. One hit was identified, namely 1,2-dihexanoyl-glycero-N-(3-(tetradecanoylamino)propyl)phosphoramidate (AHP-71B) which showed inhibitory activity and may serve as template for further structure-activity developments. Furthermore, it was found that NAPE-PLD was activated by phosphatidylethanolamine and inhibited by the beta-lactamase substrate nitrocefin.
KW - Former Faculty of Pharmaceutical Sciences
U2 - 10.1016/j.chemphyslip.2009.08.005
DO - 10.1016/j.chemphyslip.2009.08.005
M3 - Journal article
C2 - 19715685
VL - 162
SP - 53
EP - 61
JO - Chemistry and Physics of Lipids
JF - Chemistry and Physics of Lipids
SN - 0009-3084
IS - 1-2
ER -
ID: 15684957