Verma Yogesh Kumar, Reddy Bonam Srinivasa, Pawar Mithun S, Bhunia Debabrata, Sampath Kumar Halmuthur M
Vaccine Immunology Laboratory, Natural Products Chemistry Division, Indian Institute of Chemical Technology , Hyderabad 500007, India.
Vaccine Immunology Laboratory, Natural Products Chemistry Division, Indian Institute of Chemical Technology, Hyderabad 500007, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
ACS Med Chem Lett. 2015 Dec 10;7(2):172-6. doi: 10.1021/acsmedchemlett.5b00340. eCollection 2016 Feb 11.
Replacement of the amide moiety in the structure of α-GalCer with a 1,2,3-triazole linker is known to elicit a response skewed toward Th2 immunity, and glycolipids containing an aromatic ring in the terminus of their acyl or phytosphingosine structural component exhibit an enhanced Th1 immune response. In the current study, synthesis and immunological screening of a focused library of benzyloxyalkyl-substituted 1,2,3-triazolyl α-GalCer analogues are reported. The novel α-GalCer analogues activate invariant natural killer T (iNKT) cells via CD1d mediated presentation, which was confirmed by in vitro tests performed on iNKT hybridomas incubated with CD1d proteins. When tested on isolated murine splenocytes, the T1204B and T1206B compounds stimulated higher levels of both IFN-γ and IL-4 cytokine expression in vitro compared to that of α-GalCer.
已知用1,2,3 - 三唑连接体取代α - GalCer结构中的酰胺部分会引发偏向Th2免疫的反应，并且在其酰基或植物鞘氨醇结构成分末端含有芳香环的糖脂表现出增强的Th1免疫反应。在本研究中，报道了苄氧基烷基取代的1,2,3 - 三唑基α - GalCer类似物聚焦文库的合成及免疫筛选。新型α - GalCer类似物通过CD1d介导的呈递激活不变自然杀伤T（iNKT）细胞，这通过对与CD1d蛋白孵育的iNKT杂交瘤进行的体外试验得到证实。当在分离的小鼠脾细胞上进行测试时，与α - GalCer相比，T1204B和T1206B化合物在体外刺激了更高水平的IFN - γ和IL - 4细胞因子表达。
