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Novel Synthesis of Potent Site-Specific Phospholipase A2 Inhibitors

  • Ronald L. Magolda
  • William C. Ripka
  • William Galbraith
  • Paul R. Johnson
  • Marla S. Rudnick
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

Phospholipase A2 (PLA2) is an esterase responsible for the liberation of phospholipid-bound arachidonic acid, a biosynthetic precursor of putative inflammatory mediators. Arachidonic acid is metabolized by cyclooxygenase and lipoxygenase to the corresponding prostaglandins and leukotrienes (Fig. 1). Traditional antiinflammatory therapy has relied on cyclooxygenase and more recently on lipoxygenase blockade (Shen, 1981), but direct control of arachidonic acid pools has remained relatively unexplored. Recent evidence (Hirata et al., 1980; Blackwell et al., 1980; Rothhut et al., 1983) demonstrates that antiinflammatory steroids control polyunsaturated fatty acid release at both cyclooxygense and lipoxygenase pathways by enhancing the production of PLA2 inhibitory proteins (lipomodulin, macrocortin, renocortin). Direct phospholipase A2 site-specific inhibition, therefore, offers new opportunities in antiinflammatory treatment.

Keywords

Arachidonic Acid Phosphorus Oxychloride Cyclic Phosphate Fatty Acid Release EI20 EI20 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • Ronald L. Magolda
    • 1
  • William C. Ripka
    • 2
  • William Galbraith
    • 2
  • Paul R. Johnson
    • 1
  • Marla S. Rudnick
    • 2
  1. 1.Central Research and DevelopmentE. I. DuPont de Nemours and Co.WilmingtonUSA
  2. 2.Biomedical Products DepartmentE. I. DuPont de Nemours and Co.WilmingtonUSA

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