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Synthesis and evaluation of stimulatory properties of Sphingomonadaceae glycolipids

Nature Chemical Biology volume 3, pages 559–564 (2007)Cite this article

Abstract

Glycosphingolipids (GSLs) from the Sphingomonadaceae family of bacteria have been reported to be potent stimulators of natural killer T cells. These glycolipids include mono-, tri- and tetraglycosylceramides. Here we have prepared the GSL-1 to GSL-4 series of glycolipids and tested their abilities to stimulate natural killer T cells. Among these glycolipids, only GSL-1 (1) is a potent stimulator. Using a series of synthetic diglycosylceramides, we show that oligoglycosylceramides from Sphingomonadaceae are not effectively truncated to GSL-1 in lysosomes in antigen-presenting cells, possibly because the higher-order GSLs are poor substrates for lysosomal acyltransfer enzymes.

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Figure 1: Structures of potential NKT-cell agonists.
Figure 2: Only GSL-1 and PBS57 cause significant stimulation of NKT cells.
Figure 3: GlcNAc from α-GlcNAc-(1-4)-α-GalCer is truncated by lysomal processing to generate a stimulatory glycolipid.

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Acknowledgements

We acknowledge financial support from the National Institutes of Health (NIAID AI053725). J.M. is a Cancer Research Institute fellow and was supported by a grant from the Lupus Research Institute. A.B. is a Howard Hughes Medical Institute Investigator.

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Author notes

  1. Xiangtian Long and Shenglou Deng: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Chemistry and Biochemistry, C100 BNSN, Brigham Young University, Provo, 84602, Utah, USA

    Xiangtian Long, Shenglou Deng, Zhuo Zang, Nathan McNary, Randal D Goff & Paul B Savage

  2. Department of Pathology, 57 East 7th Street, University of Chicago, Chicago, 60637, Illinois, USA

    Jochen Mattner & Albert Bendelac

  3. Department of Melanoma Medical Oncology, University of Texas M.D. Anderson Cancer Center, 7455 Fannin Street, Houston, 77054, Texas, USA

    Dapeng Zhou

  4. Immunology Department, 10550 North Torrey Pines Road, Scripps Research Institute, La Jolla, 92037, California, USA

    Luc Teyton

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Contributions

X.L., S.D., Z.Z. and R.D.G. synthesized glycolipids; J.M. and D.Z determined NKT cell stimulatory activity of glycolipids; N.M. isolated glycolipids; L.T., A.B. and P.B.S. designed the project.

Corresponding author

Correspondence to Paul B Savage.

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The authors declare no competing financial interests.

Supplementary information

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Supplementary Figs. 1–5, Supplementary Scheme 1 and Supplementary Methods (PDF 4072 kb)

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Long, X., Deng, S., Mattner, J. et al. Synthesis and evaluation of stimulatory properties of Sphingomonadaceae glycolipids. Nat Chem Biol 3, 559–564 (2007). https://doi.org/10.1038/nchembio.2007.19

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