Giménez-Bastida Juan A, Suzuki Takashi, Sprinkel Katie C, Boeglin William E, Schneider Claus
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.
Prostaglandins Other Lipid Mediat. 2017 Sep;132:41-46. doi: 10.1016/j.prostaglandins.2016.09.001. Epub 2016 Sep 3.
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.
半缩酮（HK）类二十烷酸HKE和HKD是5-脂氧合酶和环氧化酶-2途径生物合成交叉产生的主要产物。它们由体外活化的人白细胞形成，因此，可能作为自分泌或旁分泌介质参与炎症反应的调节。HKE和HKD没有商业供应，迄今为止，尚未报道其全化学合成方法。有限的可得性阻碍了对其生物学效应的表征。在此，我们描述了一种通过重组人环氧化酶-2与化学合成的5S-HETE反应仿生制备HKE和HKD的方法。我们发现HKE不会诱导或抑制人THP-1单核细胞和佛波酯处理衍生的巨噬细胞释放TNFα和IL-1β。
