Synthesis of truncated analogues of the iNKT cell agonist, alpha-galactosyl ceramide (KRN7000), and their biological evaluation.

摘要

Stimulation of iNKT cells by alpha-galactosyl ceramide (alpha-GalCer), also known as KRN7000, and its truncated analogue OCH induces both Th1- and Th2-cytokines, with OCH inducing a Th2-cytokine bias. Skewing of the iNKT cells' response towards either a Th1- or Th2-cytokine profile offers potential therapeutic benefits. The length of both the acyl and the sphingosine chains in alpha-galactosyl ceramides is known to influence the cytokine release profile. We have synthesized analogues of alpha-GalCer with truncated sphingosine chains for biological evaluation, with particular emphasis on the Th1/Th2 distribution. Starting from a common precursor, d-lyxose, the sphingosine derivatives were synthesised via a straightforward Wittig condensation.