Synthesis and Immunological Activity of Novel Oligo(ethylene glycol) Analogues of α-Galactosylceramide.

CD1d-arbitrated activation of i-NKT cells by α-galactosylceramide results in the effective secretion of Th1 and Th2 cytokines, with adjuvanticity skewed toward Th2 immunity. However, the polarization of immune response could be achieved by suitable modification of the glycolipid structure. In the current study, novel glycolipids with an amphiphilic oligo ethylene glycol lipid moiety bearing the benzyloxy group at the terminus on the acyl arm of sphingosine, exhibited CD1d ligand binding as quantified by IL-2 cytokine production.

Design, Synthesis, and Immunological Evaluation of Benzyloxyalkyl-Substituted 1,2,3-Triazolyl α-GalCer Analogues.

Replacement of the amide moiety in the structure of α-GalCer with a 1,2,3-triazole linker is known to elicit a response skewed toward Th2 immunity, and glycolipids containing an aromatic ring in the terminus of their acyl or phytosphingosine structural component exhibit an enhanced Th1 immune response. In the current study, synthesis and immunological screening of a focused library of benzyloxyalkyl-substituted 1,2,3-triazolyl α-GalCer analogues are reported. The novel α-GalCer analogues activate invariant natural killer T (iNKT) cells via CD1d mediated presentation, which was confirmed by in vitro tests performed on iNKT hybridomas incubated with CD1d proteins.