Synthesis and Evaluation of N-Acetyl-2-amino-2-deoxy-α-D-galactosyl 1-Thio-7-oxaceramide, a New Analogue of α-D-Galactosyl Ceramide

✍ Scribed by Roshini Rajan; Thresen Mathew; Radovan Buffa; Frédéric Bornancin; Marco Cavallari; Peter Nussbaumer; Gennaro De Libero; Andrea Vasella

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: German
• Weight: 274 KB
• Volume: 92
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.200800454

✦ Synopsis

Abstract

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The N‐acetyl‐2‐amino‐2‐deoxy‐α‐D‐galactopyranosyl 1‐thio‐7‐oxaceramide 1 was synthesized by substituting the 7‐oxasphingosine triflate 3 with α‐D‐N‐acetyl‐1‐thiogalactosamine (2). The triflate 3 was obtained from azide 4. Thiol 2 was prepared according to a known procedure from α‐D‐galactosamine hydrochloride. As compared to ceramide (Cer), 1 is neither a substrate of ceramide kinase (CerK), consistent with the absence of the C(1)OH group, nor an inhibitor of Cer phosphorylation by CerK. While 1 partially displaced CD1d‐bound lipids, it failed to stimulate invariant natural killer T (iNKT) cells when presented by human CD1d‐transfected cells. These results suggest that 1 binds weakly to recombinant CD1d, but does not form immunogenic complexes with CD1d.