Abstract
| - The phytosphingosine-containing α-galactosylceramides (α-GalCers), KRN7000 and OCH, have beenshown to activate NKT cells via interaction with CD1d, a member of the CD1 family of antigenpresenting proteins. Evidence from KRN7000 stimulation of NKT cells suggests that α-GalCersmay have applications in the treatment or prevention of a range of viral, bacterial, and autoimmuneconditions. Moreover, OCH, a truncated analogue of KRN7000, appears to induce a TH2 bias, whichcould have implications for the treatment of autoimmune and inflammatory conditions. We haveprepared the direct sphinganine-containing analogues of KRN7000 and OCH, 1 and 2, and foundthem to be comparable in activity to the parent compounds in inducing the release of IL-2, IL-4,and IFNγ. In addition, compound 2 leads to a cytokine bias similar to that seen with OCH. This issignificant because sphinganines are more easily accessed than phytosphingosines, which shouldfacilitate SAR studies.
|