Scientific Reports (Jun 2017)

Galactosylsphingamides: new α-GalCer analogues to probe the F’-pocket of CD1d

  • Joren Guillaume,
  • Jing Wang,
  • Jonas Janssens,
  • Soumya G. Remesh,
  • Martijn D. P. Risseeuw,
  • Tine Decruy,
  • Mathy Froeyen,
  • Dirk Elewaut,
  • Dirk M. Zajonc,
  • Serge Van Calenbergh

DOI
https://doi.org/10.1038/s41598-017-04461-7
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 18

Abstract

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Abstract Invariant Natural Killer T-cells (iNKT-cells) are an attractive target for immune response modulation, as upon CD1d-mediated stimulation with KRN7000, a synthetic α-galactosylceramide, they produce a vast amount of cytokines. Here we present a synthesis that allows swift modification of the phytosphingosine side chain by amidation of an advanced methyl ester precursor. The resulting KRN7000 derivatives, termed α-galactosylsphingamides, were evaluated for their capacity to stimulate iNKT-cells. While introduction of the amide-motif in the phytosphingosine chain is tolerated for CD1d binding and TCR recognition, the studied α-galactosylsphingamides showed compromised antigenic properties.