Biomimetic synthesis of hemiketal eicosanoids for biological testing.
The hemiketal (HK) eicosanoids HKE2and HKD2are 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. HKE2and HKD2are 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 HKE2and HKD2by reaction of recombinant human cyclooxygenase-2 with chemically synthesized 5S-HETE. We found that HKE2did not induce or inhibit the release of TNFα and IL-1β by human THP-1 monocytes and phorbol ester treatment-derived macrophages.
Department of Pharmacology and Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical School, Nashville, TN 37232, U.S.A, USA.
Juan A
JA
Giménez-Bastida
Department of Pharmacology and Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical School, Nashville, TN 37232, U.S.A, USA.
Takashi
T
Suzuki
Department of Pharmacology and Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical School, Nashville, TN 37232, U.S.A, USA.
Katie C
KC
Sprinkel
Department of Pharmacology and Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical School, Nashville, TN 37232, U.S.A, USA.
William E
WE
Boeglin
Department of Pharmacology and Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical School, Nashville, TN 37232, U.S.A, USA. Electronic address: claus.schneider@vanderbilt.edu.
Claus
C
Schneider
D000447:Aldehydes / Q000737:chemistry; D032701:Biomimetics; D060326:Chemistry Techniques, Synthetic; D016207:Cytokines / Q000378:metabolism; D015777:Eicosanoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007659:Ketones / Q000737:chemistry; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism
D000447:Aldehydes; D016207:Cytokines; D015777:Eicosanoids; D007659:Ketones
Cyclooxygenase; Cytokine; Di-endoperoxide; Hemiketal; Lipoxygenase; Macrophage