Novel synthesis of α-galactosyl-ceramides and confirmation of their powerful NKT cell agonist activity
- 作者：Adrianne Lee ; Kathryn J. Farr ; Nina Dickgreber ; Colin M. Hayman ; Stefan Jü ; rs ; Ian F. Hermans ; Gavin F. Painter
- 关键词：α ; -Galactosyl-ceramide ; iNKT cells ; Lipid antigen presentation ; CD1d ; Agelasphins ; KRN 7000
- 刊名：Carbohydrate Research
- 出版年：2006
- 期刊代码：15_00086215
- 类别：ch
- 出版时间：11 December 2006
- 卷：341
- 期：17
- 页码：2785-2798
- 文件大小：363 K
摘要
α-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 α-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 α-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.