Format

Send to

Choose Destination
J Antibiot (Tokyo). 2019 Jun;72(6):498-506. doi: 10.1038/s41429-019-0180-1. Epub 2019 Apr 15.

Synthesis of chemically edited derivatives of the endogenous regulator of inflammation 9-PAHSA.

Author information

1
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0934, USA.
2
Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA, 92037-1002, USA.
3
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0934, USA. drsiegel@ucsd.edu.

Abstract

Fatty acid esters of hydroxy fatty acids (FAHFAs) are a growing class of natural products found in organisms ranging from plants to humans. The roles these endogenous derivatives of fatty acids play in biology and their novel pathways for controlling inflammation have increased our understanding of basic human physiology. FAHFAs incorporate diverse fatty acids into their structures, however, given their recent discovery non-natural derivatives have not been a focus and as a result structure-activity relationships remain unknown. The importance of the long chain hydrocarbons extending from the ester linkage as they relate to anti-inflammatory activity is unknown. Herein the systematic removal of carbons from either the hydroxy fatty acid or fatty acid regions of the most studied FAHFA, palmitic acid ester of 9-hydroxystearic acid (9-PAHSA), was achieved and these synthetic, abridged analogs were tested for their ability to attenuate IL-6 production. Reduction of the carbon chain lengths of the 9-hydroxystearic acid portion or palmitic acid hydrocarbon chain resulted in lower molecular weight analogs that maintained anti-inflammatory activity or in one case enhanced activity.

PMID:
30988370
PMCID:
PMC6784544
[Available on 2020-06-01]
DOI:
10.1038/s41429-019-0180-1
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center