2. Academic Validation
  3. Mass spectrometry-directed structure elucidation and total synthesis of ultra-long chain (O-acyl)-ω-hydroxy fatty acids

Mass spectrometry-directed structure elucidation and total synthesis of ultra-long chain (O-acyl)-ω-hydroxy fatty acids

  • J Lipid Res. 2018 Aug;59(8):1510-1518. doi: 10.1194/jlr.M086702.
Sarah E Hancock 1 2,  Ramesh Ailuri 2 3,  David L Marshall 4,  Simon H J Brown 2 5,  Jennifer T Saville 3,  Venkateswara R Narreddula 4,  Nathan R Boase 6,  Berwyck L J Poad 4,  Adam J Trevitt 3,  Mark D P Willcox 7,  Michael J Kelso 2 3,  Todd W Mitchell 8 2,  Stephen J Blanksby 9 6
Affiliations

Affiliations

  • 1 School of Medicine, University of Wollongong, Wollongong, New South Wales, Australia.
  • 2 Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, New South Wales, Australia.
  • 3 School of Chemistry, University of Wollongong, Wollongong, New South Wales, Australia.
  • 4 Central Analytical Research Facility, Institute for Future Environments Queensland University of Technology, Brisbane, Queensland, Australia.
  • 5 School of Biological Sciences, University of Wollongong, Wollongong, New South Wales, Australia.
  • 6 School of Chemistry, Physics, and Mechanical Engineering, Queensland University of Technology, Brisbane, Queensland, Australia.
  • 7 School of Optometry and Vision Science, University of New South Wales, Sydney, New South Wales, Australia.
  • 8 School of Medicine, University of Wollongong, Wollongong, New South Wales, Australia toddm@uow.edu.au stephen.blanksby@qut.edu.au.
  • 9 Central Analytical Research Facility, Institute for Future Environments Queensland University of Technology, Brisbane, Queensland, Australia toddm@uow.edu.au stephen.blanksby@qut.edu.au.
PMID: 29907595 DOI: 10.1194/jlr.M086702
Abstract

The (O-acyl)-ω-hydroxy FAs (OAHFAs) comprise an unusual lipid subclass present in the skin, vernix caseosa, and meibomian gland secretions. Although they are structurally related to the general class of FA esters of hydroxy FAs (FAHFAs), the ultra-long chain (30-34 carbons) and the putative ω-substitution of the backbone hydroxy FA suggest that OAHFAs have unique biochemistry. Complete structural elucidation of OAHFAs has been challenging because of their low abundance within complex lipid matrices. Furthermore, because these compounds occur as a mixture of closely related isomers, insufficient spectroscopic data have been obtained to guide structure confirmation by total synthesis. Here, we describe the full molecular structure of ultra-long chain OAHFAs extracted from human meibum by exploiting the gas-phase purification of lipids through multi-stage MS and novel multidimensional ion activation methods. The analysis elucidated sites of unsaturation, the stereochemical configuration of carbon-carbon double bonds, and ester linkage regiochemistry. Such isomer-resolved MS guided the first total synthesis of an ultra-long chain OAHFA, which, in turn, confirmed the structure of the most abundant OAHFA found in human meibum, OAHFA 50:2. The availability of a synthetic OAHFA opens new territory for future investigations into the unique biophysical and biochemical properties of these lipids.

Keywords

chemical synthesis; eye; fatty acid esters of hydroxy fatty acids; meibum; secretion; tandem mass spectrometry.

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