Enzymatic studies with 3-oxa n-3 DPA

Maria K Pangopoulos; Jens M N Nolsøe; Simen G Antonsen; Romain A Colas; Jesmond Dalli; Marius Aursnes; Yngve Stenstrøm; Trond Vidar Hansen

doi:10.1016/j.bioorg.2020.103653

Enzymatic studies with 3-oxa n-3 DPA

Bioorg Chem. 2020 Mar:96:103653. doi: 10.1016/j.bioorg.2020.103653. Epub 2020 Feb 8.

Authors

Maria K Pangopoulos¹, Jens M N Nolsøe¹, Simen G Antonsen¹, Romain A Colas², Jesmond Dalli³, Marius Aursnes⁴, Yngve Stenstrøm¹, Trond Vidar Hansen⁵

Affiliations

¹ Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, PO Box 5003, 1432 Ås, Norway.
² Lipid Mediator Unit, Center for Biochemical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
³ Lipid Mediator Unit, Center for Biochemical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK; Centre for Inflammation and Therapeutic Innovation, Queen Mary University of London, London, UK.
⁴ Department of Pharmacy, Section of Pharmaceutical Chemistry, University of Oslo, PO Box 1068 Blindern, N-0316 Oslo, Norway.
⁵ Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, PO Box 5003, 1432 Ås, Norway; Department of Pharmacy, Section of Pharmaceutical Chemistry, University of Oslo, PO Box 1068 Blindern, N-0316 Oslo, Norway. Electronic address: t.v.hansen@farmasi.uio.no.

PMID: 32062066
DOI: 10.1016/j.bioorg.2020.103653

Abstract

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.

Keywords: 3-oxa n-3 DPA; Biosynthesis; Cyclooxygenase-2; Lipids; Lipoxygenases; Oxygenated products; Polyunsaturated fatty acids; Specialized pro-resolving lipid mediators.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Arachidonate 12-Lipoxygenase / metabolism*
Arachidonate 15-Lipoxygenase / metabolism*
Arachidonate 5-Lipoxygenase / metabolism*
Cyclooxygenase 2 / metabolism*
Fatty Acids, Unsaturated / metabolism*
Glycine max / enzymology
Glycine max / metabolism
Humans
Mice
Substrate Specificity

Substances

Fatty Acids, Unsaturated
Arachidonate 12-Lipoxygenase
Arachidonate 15-Lipoxygenase
Arachidonate 5-Lipoxygenase
Cyclooxygenase 2
docosapentaenoic acid

Grants and funding

107613/Z/15/Z/WT_/Wellcome Trust/United Kingdom