Enzymatic studies with 3-oxa n-3 DPA

• Published in: Bioorganic chemistry Vol. 96; pp. 103653 - 103659
• Main Authors: Pangopoulos, Maria K., Nolsøe, Jens M.N., Antonsen, Simen G., Colas, Romain A., Dalli, Jesmond, Aursnes, Marius, Stenstrøm, Yngve, Hansen, Trond Vidar
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.03.2020; Elsevier
• Subjects: 3-oxa n-3 DPA; Animals; Arachidonate 12-Lipoxygenase - metabolism; Arachidonate 15-Lipoxygenase - metabolism; Arachidonate 5-Lipoxygenase - metabolism; Biochemistry & Molecular Biology; Biosynthesis; Chemistry; Chemistry, Organic; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Fatty Acids, Unsaturated - metabolism; Glycine max - enzymology; Glycine max - metabolism; Humans; Life Sciences & Biomedicine; Lipids; Lipoxygenases; Mice; Oxygenated products; Physical Sciences; Polyunsaturated fatty acids; Science & Technology; Specialized pro-resolving lipid mediators; Substrate Specificity; Lipoxygenases; 3-oxa n-3 DPA; Oxygenated products; Polyunsaturated fatty acids; Specialized pro-resolving lipid mediators; Lipids; Biosynthesis; Cyclooxygenase-2; RESOLUTION; FATTY-ACIDS; LIPID MEDIATORS; ARACHIDONIC-ACID; LIPOXYGENASE; RESOLVINS; DOCOSAHEXAENOIC ACID; INFLAMMATION; STEREOSELECTIVE-SYNTHESIS; NEUROPROTECTIN-D1
• ISSN: 0045-2068; 1090-2120; 1090-2120
• DOI: 10.1016/j.bioorg.2020.103653

[Display omitted] •Design and synthesis of 3-oxa n-3 DPA reported.•3-oxa n-3 DPA is a synthetic mimic of n-3 docosapentaenoic acid.•This polyunsaturated fatty acid mimic is a substrate for several oxygenase enzymes.•LC/MS-MS analyses were used for product identification.•E,Z-configured allylic secondary alcohols were formed in all oxygenases used. Cyclooxygenase-2 and several lipoxygenases convert polyunsaturated fatty acids into a large variety of products. During inflammatory processes, these enzymes form several distinct families of specialized pro-resolving lipid mediators possessing potent anti-inflammatory and pro-resolving effects. These mediators have attracted a great interest as leads in drug discovery and have recently been the subject of biosynthetic pathway studies using docosahexaenoic and n-3 docosapentaenoic acid as substrates. Herein we present enzymatic studies with cyclooxygenase-2 and 5-, 12- and 15-lipoxygenase enzymes using 3-oxa n-3 DPA as a synthetic mimic of n-3 docosapentaenoic acid. Structural elucidation based on data from RP-HPLC UV and LC/MS-MS experiments enabled the identification of novel enzymatically formed products. These findings constitute the basis for further biosynthetic studies towards understanding the mechanisms regulating substrate utilization in the biosynthesis of specialized pro-resolving lipid mediators.