| Research Abstract |
It was supposed as one of the mechanisms for immuno-suppression in cancer patients that macrophage activating factor (Gc MAF) could not be produced from a precursor, serum vitamin D-binding protein (Gc protein) due to deglycosylation by a-N-acetyl galactosaminidase (α-NaGalase). It was reported that α-NaGalase increased in cancer patients serum (Yamamoto, N. et al., 1998). To develop a immuno modulator of cancer therapy, the mechanism of immuno-suppression was defined by characterization of α-NaGalase in various tumor cells and α-NaGalase inhibitors was designed and synthesized as immuno potentiator.
1) α-NaGalase activities in tumor cell lysates from Hep G2 and HCT116 cells and normal cell lysates from Chang liver cell and isolated rat hepatocytes were measured. A high specific activity of a-NaGalase was found in tumor cell lines compare to normal cells. Because α-NaGalase deglycosylated exo-type substrate specifically, it was necessary to reinvestigate the deactivation mechanism of GcMAF by a-NaGalase.
2) Azasugar derivatives introduced spィイD12ィエD1 carbon to control a torsional angle between hydroxyl groups were designed and synthesized as a α-NaGalase inhibitor and an immunopotentiator, because a sugar-shaped alkaloid, swainsonine, was a α-mannosidase inhibitor and an immunopotentiator. Their activities of α-NaGalase inhibition and macrophage activation are now under investigation.
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