Synthesis and biological activity of α-galactosyl ceramide KRN7000 and galactosyl (α1→2) galactosyl ceramide

Veerapen et al.

Abstract

We herein report a faster and less cumbersome synthesis of the biologically attractive, α-galactosyl
ceramide (α-GalCer), known as KRN7000, and its analogues. More importantly, the use of a silicon
tethered intramolecular glycosylation reaction gave easy access to the diglycosyl ceramide Gal
(α1→2)GalCer, which has been shown to require uptake and processing to the biologically active
α-GalCer derivative.

Keywords

CD1d; KRN7000; iNKT; Galactosyl(α1-2)galactosyl

CD1d is a nonpolymorphic glycoprotein expressed on the surface of antigen-presenting cells
(APCs). It is specifically associated with presenting lipid antigens that activate the distinctive
class of T cells, known as invariant Natural Killer T (iNKT) cells. iNKT cells display
characteristics of both T cells and NK cells and play a crucial role in diverse immune responses
and other pathologic conditions. When the synthetic glycolipid α-galactosyl ceramide (α-
GalCer), known as KRN7000 (1), is bound to CD1d and presented to the T cell receptors
(TCRs) on the surface of iNKT cells, the latter are activated to release diverse cytokines,
including both Th1 and Th2 cytokines. It is believed that the release of Th1 cytokines may
contribute to antitumour and antimicrobial functions while that of Th2 cytokines may help
alleviate autoimmune diseases such as multiple sclerosis and arthritis. α-GalCer and its
derivatives have proved to be and remain invaluable tools in understanding the functioning of
CD1d and NKT cells in a wide range of immune responses. As part of various ongoing studies,
easy access to relatively extensive quantities of these substrates is, therefore, required.

Published as: BioorgMed Chem Lett. 2009 August 01; 19(15): 4288-4291.

<<   1   2   3   4   5   >>

More intriguing information