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Capture and release of alkyne-derivatized glycerophospholipids using cobalt chemistry

Nature Chemical Biology volume 6, pages 205–207 (2010)Cite this article

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Abstract

Alkyne-modified phospholipids can be unambiguously identified and differentiated from native species in complex mixtures by formation of dicobalthexacarbonyl complexes. This reaction is specific for alkynes and is unaffected by other glycerophospholipid-related moieties. Enrichment of cells with alkyne-derivatized fatty acids or glycerophospholipids followed by solid-phase sequestration and release is a promising new method for unequivocally monitoring individual glycerophospholipids following incorporation into cells. This technique also facilitates lipidomic analysis of substrates and products.

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Figure 1: LC/MS results from PC 3–enriched RAW 264.7 cell extracts.
Figure 2: Capture and release of alkyne-modified lipids.

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Acknowledgements

The authors thank P. Ivanova and D. Myers for technical assistance and many helpful conversations. This work was partially supported by the US National Institutes of Health (P01-ES013125 to H.A.B., L.J.M. and N.A.P.), a Vanderbilt Institute of Chemical Biology Pilot Program grant (H.A.B. and N.A.P.) and National Institutes of Health Grant Lipid Maps U54 GM69338 (H.A.B.).

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Author notes

  1. Stephen B Milne and Keri A Tallman: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, USA

    Stephen B Milne, Michelle D Armstrong, Lawrence J Marnett & H Alex Brown

  2. Department of Chemistry, Vanderbilt University, Nashville, Tennessee, USA

    Keri A Tallman, Remigiusz Serwa, Lawrence J Marnett, Charles M Lukehart, Ned A Porter & H Alex Brown

  3. Department of Biochemistry, Vanderbilt University, Nashville, Tennessee, USA

    Carol A Rouzer, Lawrence J Marnett, Ned A Porter & H Alex Brown

  4. Vanderbilt Institute for Chemical Biology, Vanderbilt University, Nashville, Tennessee, USA

    Lawrence J Marnett, Ned A Porter & H Alex Brown

  5. Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, USA

    Lawrence J Marnett & H Alex Brown

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  1. Stephen B Milne
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Contributions

S.B.M. analyzed cell extract samples by mass spectrometry. K.A.T. and R.S. performed chemical synthesis, purification and analysis. S.B.M. and C.M.L. developed the alkyne lipid cobalt derivatization protocol. K.A.T. and S.B.M. developed the capture and release methodology. M.D.A. and C.A.R. contributed to the lipid enrichment procedures. L.J.M., N.A.P. and H.A.B. were responsible for overall project direction and experimental design. All authors discussed the results and modified the manuscript.

Corresponding author

Correspondence to H Alex Brown.

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The authors declare no competing financial interests.

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Milne, S., Tallman, K., Serwa, R. et al. Capture and release of alkyne-derivatized glycerophospholipids using cobalt chemistry. Nat Chem Biol 6, 205–207 (2010). https://doi.org/10.1038/nchembio.311

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