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Synfacts 2023; 19(01): 0085
DOI: 10.1055/s-0042-1751775
Innovative Drug Discovery and Development

Photoaffinity Lipid Probes Decipher Docosahexanoic Acid Target

Contributor(s):
Dirk Trauner
,
Tufan K. Mukhopadhyay
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
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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.


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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.


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Publication History

Article published online:
16 December 2022

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