van der Stelt M.
* et al.
Leiden University and Oncode Institute, The Netherlands
Comparative Photoaffinity Profiling of Omega‑3 Signaling Lipid Probes Reveals Prostaglandin
Reductase 1 as a Metabolic Hub in Human Macrophages.
J. Am. Chem. Soc. 2022;
144: 18938-18947
DOI:
10.1021/jacs.2c06827
Key words
omega-3 fatty acids - bio-orthogonal lipid probes - Wittig olefination
Significance
Docosahexanoic acid (DHA) is an omega-3-polyunsaturated fatty acid (PUFA) and an endogenous
signaling lipid with anti-inflammatory properties. However, its biological mechanism
in the resolution of inflammation is poorly understood. Here, the authors developed
two bio-orthogonal photoaffinity-click (pac) probes, pac-DHA and its 17-hydroxy metabolite pac-17-HDHA, to identify
their targets in human macrophages.
Comment
The authors synthesized the PUFAs using Wittig olefination as a key reaction. Photoaffinity-based
protein profiling revealed prostaglandin reductase 1 as the lipid-binding partner,
which metabolizes 17-oxo-DHA – a metabolite of 17-HDHA. The authors also found that
17-oxo-DHA reduces the formation of pro-inflammatory lipids in human macrophages and
neutrophils.
