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Galactosylsphingamides: new ?-GalCer analogues to probe the F'-pocket of CD1d.

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 ?-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 ?-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 ?-galactosylsphingamides showed compromised antigenic properties.

SUBMITTER: Guillaume J

PROVIDER: S-EPMC5487351 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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

Guillaume Joren J Wang Jing J Janssens Jonas J Remesh Soumya G SG Risseeuw Martijn D P MDP Decruy Tine T Froeyen Mathy M Elewaut Dirk D Zajonc Dirk M DM Calenbergh Serge Van SV

Scientific reports 20170627 1

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. W ...[more]

PMID: 28655912

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