The novel lipid mediator PD1n-3 DPA: An overview of the structural elucidation, synthesis, biosynthesis and bioactions

Abstract

Resolvins, protectins and maresins are individual families of specialized pro-resolving mediators biosynthesized from the dietary n-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid. These enzymatically oxygenated polyunsaturated lipid mediators were first elucidated during the resolution phase of acute inflammation in animal models of self-limited inflammation. Specialized pro-resolving mediators display potent bioactions when administrated in vivo. Biosynthetic pathway studies have revealed that individual lipoxygenases and cyclooxygenase-2 converts eicosapentaenoic acid and docosahexaenoic acid into distinct families of the resolvins, protectins and maresins. Recently n-3 docosapentaenoic acid was found to be a substrate for the biosynthesis of several novel families of specialized pro-resolving mediators. One example is PD1_{n-3 DPA}. During the 6th European Workshop on Lipid Mediators, Frankfurt, Germany, the structural elucidation, total organic synthesis, studies on the biosynthetic pathway, as well as the potent anti-inflammatory and pro-resolving properties of PD1_{n-3 DPA} were presented. Herein, we provide an overview of these topics for the new member PD1_{n-3 DPA} of the super-family of pro-resolving mediators.

Keywords: Anti-inflammatory; Human leukocytes; Lipoxygenase; Pro-resolution; Protectin D1(n-3 DPA); Specialized pro-resolving mediators; n-3 Docosapentaenoic acid.

Fig. 1

The chemical structures of eicosapentaenoic acid, docosahexaenoic acid, n-3 docosapentaenoic acid and an outline of the individual families of SPMs biosynthesized from these n-3 PUFAs.

Fig. 2

Chemical structures of protectin D1 (PD1), maresin 1 (MaR1) and resolvin D1 biosynthesized from DHA, and the novel SPM PD1_{n-3 DPA} biosynthesized from n-3 DPA.

Fig. 3

Biosynthetic pathway for PD1_{n-3 DPA}. For details on the individual enzymatic steps in the biosynthesis of oxygenated PUFAs, the readers should consult reference [24] and [41].

Fig. 4

Outline of the formation of the four methanol trapping products formed, their chemical structures and the putative carbocation intermediate involved.

Fig. 5

Examples of biosynthetic pathways for mediators in inflammation-resolution in which epoxides are intermediates. Only the chemical structures of the DHA derived examples are depicted; for structures of the AA derived, see references [41, 51, 52].