P-68 ナチュラルキラー(NK)T細胞を特異的に活性化し、IFN-γに偏ったサイトカインの産生を誘導する新規糖脂質RCAI-56の合成(ポスター発表の部)

概要

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NKT cell is a potent producer of immunoregulatory cytokines. T cell receptor of NKT cell recognizes the complex of α-galactosylceramide-CD1d protein, which is the surface protein of antigen presenting cells, and the activated NKT cell can produce the both Th1 (immunostimulant) and Th2 (immunosuppressant)-type cytokines. In 1995, Kirin Brewery Co. Ltd. developed KRN7000 (2), which is a derivative of agerasphins (main component is agelasphin-9b, 1). KRN7000 is a strong stimulant to NKT cell. However, it induces both Th1 and Th2-type cytokines production of NKT cell by single stimulation. Th1 and Th2-type cytokines can antagonize each other's biological actions. Accordingly, use of KRN7000 for clinical therapy was unsuccessful. To circumvent this problem, we developed new ligand, RCAI-56 (5), which is a carbocyclic analogue of KRN7000. RCAI-56 was synthesized by coupling of carba-α-D-galactose derivative (13), synthesized from the commercially available methyl α-D-galactopyranoside, with cyclic sulfamidate derivative (15). According to bioassay (mouse, in vivo), RCAI-56 was found to be a potent stimulant of NKT cell in vivo to induce the production of Th1 biased cytokines such as IFN-γ.
天然有機化合物討論会の論文
2007-08-24