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

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-substi...

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Published in:	Journal of lipid research Vol. 59; no. 8; pp. 1510 - 1518
Main Authors:	Hancock, Sarah E., Ailuri, Ramesh, Marshall, David L., Brown, SimonH.J., Saville, Jennifer T., Narreddula, Venkateswara R., Boase, Nathan R., Poad, BerwyckL.J., Trevitt, Adam J., Willcox, MarkD.P., Kelso, Michael J., Mitchell, Todd W., Blanksby, Stephen J.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-08-2018 Journal of Lipid Research The American Society for Biochemistry and Molecular Biology Elsevier
Subjects:	chemical synthesis Chemistry Techniques, Synthetic Esters Esters - chemistry eye fatty acid esters of hydroxy fatty acids Fatty acids Fatty Acids - chemical synthesis Fatty Acids - chemistry Humans Isomers Lipids Mass Spectrometry Mass spectroscopy Meibomian Glands - chemistry meibum Purification secretion Secretions Skin Stereoisomerism tandem mass spectrometry Territory chemical synthesis eye fatty acid esters of hydroxy fatty acids meibum tandem mass spectrometry secretion
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 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.
ISSN:	0022-2275 1539-7262
DOI:	10.1194/jlr.M086702