Synthesis, Structural Confirmation, and Biosynthesis of 22-OH-PD1 n-3 DPA

Molecules. 2019 Sep 5;24(18):3228. doi: 10.3390/molecules24183228.

Abstract

PD1n-3 DPA belongs to the protectin family of specialized pro-resolving lipid mediators. The protectins are endogenously formed mediators that display potent anti-inflammatory properties and pro-resolving bioactivities and have attracted interest in drug discovery. However, few studies have been reported of the secondary metabolism of the protectins. To investigate the metabolic formation of the putative C22 mono-hydroxylated product, coined 22-OH-PD1n-3 DPA, a stereoselective synthesis was performed. LC/MS-MS data of synthetic 22-OH-PD1n-3 DPA matched the data for the biosynthetic formed product. Cellular studies revealed that 22-OH-PD1n-3 DPA is formed from n-3 docosapentaenoic acid in human serum, and we confirmed that 22-OH-PD1n-3 DPA is a secondary metabolite produced by ω-oxidation of PD1n-3 DPA in human neutrophils and in human monocytes. The results reported are of interest for enabling future structure-activity relationship studies and provide useful molecular insight of the metabolism of the protectin class of specialized pro-resolving mediators.

Keywords: 22-OH-PD1n-3 DPA; biosynthesis; natural products; omega oxidation; polyunsaturated fatty acids; protectins; specialized pro-resolving mediators; stereoselective synthesis; structural elucidation.

MeSH terms

  • Biosynthetic Pathways
  • Chemistry Techniques, Synthetic
  • Chromatography, Liquid
  • Docosahexaenoic Acids / biosynthesis
  • Docosahexaenoic Acids / chemical synthesis
  • Docosahexaenoic Acids / chemistry*
  • Humans
  • Molecular Conformation
  • Molecular Structure
  • Monocytes / immunology
  • Monocytes / metabolism
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Structure-Activity Relationship
  • Tandem Mass Spectrometry

Substances

  • 22-OH-PD1 compound
  • Docosahexaenoic Acids