title: Controlled formation of mono- and dihydroxy-resolvins from EPA and DHA using soybean 15-lipoxygenase.
abstract: Resolvins and protectins are important anti-inflammatory and pro-resolution compounds derived from the enzymatic oxidation of omega-3 fatty acids all-cis-5,8,11,14,17-eicosapentaenoic acid (EPA) and all-cis-4,7,10,13,16,19-docosahexaenoic acid (DHA). We have developed a simple, controlled method to synthesize an array of resolvin and protectin analogs from fatty acid starting materials using soybean 15-lipoxygenase. The conditions were optimized for the production of both mono- and dihydroxy derivatives, with enzyme concentration and pH found to have a significant effect on the reaction products. The methods were applied to five biologically important omega-3 and omega-6 fatty acid substrates. Mono- and dihydroxy compounds were successfully synthesized from all substrates and the products were characterized by normal phase (NP) HPLC, GC-MS, TOF-MS, UV-visible (UV-vis) spectroscopy, and NMR spectroscopy. The methods could be further applied to any polyunsaturated fatty acids containing the cis-1,4,7,10-undecatetraene moiety to produce a range of novel compounds with potential biological activity.
authors.affiliation: Centre for Chemistry and Biotechnology, Deakin University, Geelong, Victoria 3220, Australia.
authors.forename: Eleanor P
authors.initials: EP
authors.lastname: Dobson
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Barrow
authors.forename: Jaroslav A
authors.initials: JA
authors.lastname: Kralovec
authors.forename: Jacqui L
authors.initials: JL
authors.lastname: Adcock
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry; D001093:Arachidonate 15-Lipoxygenase / Q000737:chemistry* / Q000378:metabolism; D018957:CD59 Antigens / Q000737:chemistry; D004281:Docosahexaenoic Acids / Q000737:chemistry / Q000378:metabolism*; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000138:chemical synthesis / Q000737:chemistry; D013025:Glycine max / Q000201:enzymology
chemical_list: D000893:Anti-Inflammatory Agents; D018957:CD59 Antigens; D015525:Fatty Acids, Omega-3; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D001093:Arachidonate 15-Lipoxygenase; C499823:5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid