Xia Chengfeng, Yao Qingjia, Schümann Jens, Rossy Emmanuel, Chen Wenlan, Zhu Lizhi, Zhang Wenpeng, De Libero Gennaro, Wang Peng George
Department of Biochemistry, The Ohio State University, Columbus, OH 43210, USA.
Bioorg Med Chem Lett. 2006 Apr 15;16(8):2195-9. doi: 10.1016/j.bmcl.2006.01.040. Epub 2006 Feb 2.
Glycoceramides can activate NKT cells by binding with CD1d to produce IFN-gamma, IL-4, and other cytokines. An efficient synthetic pathway for alpha-galactosylceramide (KRN7000) was established by coupling a protected galactose donor to a properly protected ceramide. During the investigation, it was discovered that when the ceramide was protected with benzyl groups, only beta-galactosylceramide was produced from the glycosylation reaction. In contrast, the ceramide with benzoyl protecting groups produced alpha-galactosylceramide. Isoglobotrihexosylceramide (iGb3) was prepared by glycosylation of Galalpha1-3Galbeta1-4Glc donor with 2-azido-sphingosine in high yield. Biological assays on the synthetic KRN7000 and iGb3 were performed using human and murine iNKT cell clones or hybridomas.
糖神经酰胺可通过与CD1d结合激活NKT细胞，从而产生γ干扰素、白细胞介素-4及其他细胞因子。通过将受保护的半乳糖供体与适当保护的神经酰胺偶联，建立了α - 半乳糖神经酰胺（KRN7000）的高效合成途径。在研究过程中发现，当神经酰胺用苄基保护时，糖基化反应仅生成β - 半乳糖神经酰胺。相比之下，带有苯甲酰保护基的神经酰胺则生成α - 半乳糖神经酰胺。通过将Galα1-3Galβ1-4Glc供体与2-叠氮基鞘氨醇进行糖基化反应，以高产率制备了异球三己糖神经酰胺（iGb3）。使用人和小鼠的iNKT细胞克隆或杂交瘤对合成的KRN7000和iGb3进行了生物学测定。
