P-88 ナチュラルキラー(NK)T細胞を活性化し、IFN-γの産生を強力に誘導する新規糖脂質RCAI-61の合成(ポスター発表の部)

概要

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NKT cell is categorized as the fourth class of immunocytes, which has both NK and T cell receptors (TCR). CD1d is one of the surface proteins of antigen presenting cells. When NKT cell is activated by recognizing the complex of α-glycosylceramide-CD1d with its TCR, NKT cell can produce both Th1 (immunostimulatory) and Th2 (immunosuppressant) type cytokines in large quantities. In 1995, researchers at Kirin Brewery Co. developed KRN7000 (2), which is an analogue of agelasphins (main component is agelasphin-9b, 1) as the anticancer drug candidate. However, KRN7000 induces both Th1 and Th2 cytokines at the same time by single injection. Th1 and Th2 type cytokines can antagonize each other's biological function, and therefore use of KRN7000 for clinical therapy is limited. To circumvent this problem, we developed a new analogue, RCAI-61 (25c), which is a 6-O-methylated α-galactopyranosyl analogue of KRN7000. RCAI-61 could be easily synthesized by galactosylation of ceramide (23) with 6-O-methylated galactopyranoside intermediate (22c), which could be synthesized from commercially available methyl α-D-galactopyranoside (9). According to bioassay (mouse, in vivo), RCAI-61 was found to be a potent inducer of Th1 type cytokine production such as IFN-γ.
天然有機化合物討論会の論文
2008-09-01