title: Synthesis of truncated analogues of the iNKT cell agonist, α-galactosyl ceramide (KRN7000), and their biological evaluation.
abstract: 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.affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Natacha
authors.initials: N
authors.lastname: Veerapen
authors.forename: Faye
authors.initials: F
authors.lastname: Reddington
authors.forename: Mariolina
authors.initials: M
authors.lastname: Salio
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerundolo
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
mesh_terms: D016207:Cytokines / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D005699:Galactosylceramides / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects*
chemical_list: D016207:Cytokines; D005699:Galactosylceramides; C103873:KRN 7000