Novel synthesis of alpha-galactosyl-ceramides and confirmation of their powerful NKT cell agonist activity.
alpha-Galactosyl-ceramide (1) has been identified as a powerful modulator of immunological processes through its capacity to bind CD1d molecules and specifically activate invariant natural killer (NK)-like T cells (iNKT cells). This paper describes the synthesis of 1, the analogous alpha-galactosyl-ceramide 3, and its short chain analogue 'OCH' (2), by use of the 4,6-di-O-tert-butylsilylene (DTBS) protecting group to produce a powerful alpha-galactosylating agent. In vivo experiments confirmed these compounds to be potent and selective activators of iNKT cells in a CD1d-dependent manner, each inducing a unique profile of cytokine release. This synthesis strategy will permit the generation of novel derivatives for use in the study of the mechanism of iNKT cell activation.
Lee
Adrianne
A
Carbohydrate Chemistry, Industrial Research Limited, PO Box 31-310, Lower Hutt, New Zealand.
Farrand
Kathryn J
KJ
Dickgreber
Nina
N
Hayman
Colin M
CM
Jürs
Stefan
S
Hermans
Ian F
IF
Painter
Gavin F
GF
D000818:Animals; D005699:Galactosylceramides / Q000138:chemical synthesis* / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000276:immunology
D005699:Galactosylceramides; D007155:Immunologic Factors; C493154:alpha-galactosylceramide