Journal of Lipid Research
Volume 59, Issue 8, August 2018, Pages 1510-1518
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Research Articles
Mass spectrometry-directed structure elucidation and total synthesis of ultra-long chain (O-acyl)-ω-hydroxy fatty acids

https://doi.org/10.1194/jlr.M086702Get rights and content
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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.

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

Cited by (0)

This work was supported by Australian Research Council Grants LP140100711 (Linkage Program, with industry support from Allergan) and FT110100249 (Future Fellowship Scheme, to T.W.M.) and Queensland University of Technology support from the Central Analytical Research Facility operated by the Institute for Future Environments to S.J.B., V.R.N., N.R.B., B.L.J.P., and D.L.M; and a Postgraduate Research Award to V.R.N.

The online version of this article (available at http://www.jlr.org) contains a supplement.

Present address of S. E. Hancock: School of Medical Sciences, University of New South Wales, Sydney, Australia.

Present address of J. T. Saville: Genetics and Molecular Pathology, SA Pathology at Women's and Children's Hospital, Adelaide, South Australia, Australia.

    Abbreviations:

    AMPP

    N-(4-aminomethylphenyl)pyridinium

    CID

    collision-induced dissociation

    DHP

    dihydropyran

    FAHFA

    FA esters of hydroxy FA

    HFA

    hydroxy FA

    4-I-AMPP

    1-(3-(aminomethyl)-4-iodophenyl)pyridin-1-ium

    OAHFA

    (O-acyl)-ω-hydroxy FA

    OzID

    ozone-induced dissociation

    PD

    photodissociation

    RDD

    radical-directed dissociation

    Rf

    retention factor

    THF

    tetrahydrofuran

    THP

    tetrahydropyran

    TsOH

    p-toluene sulfonic acid

    WE

    wax ester