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

Journal article

Stimulation of iNKT cells by α-galactosyl ceramide (α-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 α-galactosyl ceramides is known to influence the cytokine release profile. We have synthesized analogues of α-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.

Authors: Veerapen, N; Reddington, F; Salio, M; Cerundolo, V; Besra, G

• Publication status: Published
• Journal: Bioorganic and medicinal chemistry
• Volume: 19
• Issue: 1
• Pages: 221-228
• Publication date: 2011-01-01
• DOI: 10.1016/j.bmc.2010.11.032
• EISSN: 1464-3391
• ISSN: 0968-0896
• Language: English
• Keywords: T-Lymphocytes; Drug Evaluation, Preclinical; Cytokines; Galactosylceramides; Killer Cells, Natural; Humans