New CD1d agonists: Synthesis and biological activity of 6鈥?triazole-substituted 伪-galactosyl ceramides
- 作者：Peter J. Jervisa ; b ; Lisa M. Grahamc ; Erin L. Fosterc ; Liam R. Coxb ; Steven A. Porcellic ; Gurdyal S. Besraa ; g.besra@bham.ac.uk
- 关键词：伪-GalCer ; CD1d ; iNKT cell ; Triazole ; Click chemistry
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2012
- 期刊代码：10_0960894x
- 类别：ch
- 出版时间：1 July, 2012
- 卷：22
- 期：13
- 页码：4348-4352
- 文件大小：416 K
摘要
Huisgen [3+2] dipolar cycloaddition of 6鈥?azido-6鈥?/strong>-deoxy-伪-galactosyl ceramide 11 with a range of alkynes (or a benzyne precursor) yielded a series of triazole-containing 伪-galactosyl ceramide (伪-GalCer) analogues in high yield. These 伪-GalCer analogues and the precursor azide 11 were tested for their ability to activate iNKT cells and stimulate IL-2 cytokine secretion in vitro, and IFN-纬 and IL-4 cytokine secretion in vivo. Some of these analogues, specifically 11, 12b, 12f and 13, were more potent IL-2 stimulators than the prototypical CD1d agonist, 伪-GalCer 1. In terms of any cytokine bias, most of the triazole-containing analogues exhibited a small Th2 cytokine-biasing response relative to that shown by 伪-GalCer 1. In contrast, the cycloaddition precursor, namely azide 11, provided a small Th1 cytokine-biasing response.