Molecular design of anticancer drug, α-NaGalase inhibitors for immunopotentiation

这是一种治疗方法，即癌症患者对免疫系统的治疗。activating factor （Gc MAF）无法produced from a precursorserum vitamin -binding protein (Gc protein) due to deglycosylation by a-N-acetyl galactosaminidaseα-NaGalase increased in cancer patients serum （Yamamoto, α-NaGalase increased in cancer patients serum）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 tumorcells and α-NaGalase inhibitors was designed and synthesized as immuno potentiator.1) α-NaGalaseactivities in tumor cell lysates from Hep G2 and HCT116 cells and normal cell lysates from Changliver cell and isolated rat hepatocytes was high specific activity of A - nagalase wasfound in tumor cell lines compare to normal cells. Because α-NaGalase deglycosylated ex -typesubstrate specifically,这是必要的reinvestigate the deactivation mechanism of GcMAF by a-NaGalase.2derivatives introduced sp D12 carbon to control a torsional angle between hydroxyl groups were设计和synthesized as a α-NaGalase inhibitor and an immunopotentiatorbecause a sugar-shaped alkaloid, swainsoninewas a α-mannosidase inhibitor and an immunopotentiator. Their activities of α-NaGalase inhibitionand macrophage activation are now under investigation。

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.