Biomimetic synthesis of hemiketal eicosanoids for biological testing.

Juan A Giménez-Bastida, Takashi Suzuki, Katie C Sprinkel, William E Boeglin, Claus Schneider

Journal: Prostaglandins & other lipid mediators 2018;132():41-46

PMID: 27596332

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Abstract

The hemiketal (HK) eicosanoids HKE and HKD are the major products resulting from the biosynthetic cross-over of the 5-lipoxygenase and cyclooxygenase-2 pathways. They are formed by activated human leukocytes ex vivo, and, therefore, may be involved in regulation of the inflammatory response as autocrine or paracrine mediators. HKE and HKD are not commercially available and, so far, no method for their total chemical synthesis has been reported. The limited availability has impeded the characterization of their biological effects. Here, we describe a method for biomimetic preparation of HKE and HKD by reaction of recombinant human cyclooxygenase-2 with chemically synthesized 5S-HETE. We found that HKE did not induce or inhibit the release of TNFα and IL-1β by human THP-1 monocytes and phorbol ester treatment-derived macrophages.

Address: Department of Pharmacology and Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical School, Nashville, TN 37232, U.S.A, USA.; Department of Pharmacology and Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical School, Nashville, TN 37232, U.S.A, USA. Electronic address: [email protected].

DOI: 10.1016/j.prostaglandins.2016.09.001