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

它是癌症患者在宏观激活因子（GcMAF）中抑制免疫抑制的机制之一，不能从预cursor、血清维生素D-结合蛋白（Gc蛋白）中产生，并通过a-N-乙酰谷氨酰胺酶（α-NaGalase）进行降解。据报道，α-NaGalase在癌症患者血清中增加（Yamamoto， N.）和其他人，一九九八年）。要开发一种癌症治疗的免疫调节剂，免疫抑制的机制是由不同肿瘤细胞和α-NaGalase抑制剂的表征定义的α-NaGalase活性，如免疫电位器设计和合成。1） α-NaGalase在肿瘤细胞溶解中的活性，从Hep G2和HCT 116细胞溶解中的正常细胞溶解，从Chang liver细胞和孤立的大鼠谷胱甘肽被测量。在肿瘤细胞线上发现了一种高特异性活性，与正常细胞线相比。因为α-NaGalase去环化外型基底特别需要重新研究GcMAF的去激活机制，因为A-NaGalase. 2）引入了Azasugar衍生物D12 Yue D1碳，以控制羟基之间的一个三角角，被设计和合成为α-NaGalase抑制剂和免疫活性剂，因为一个糖形的生物碱、swainsonine、一个α-Mansidase抑制剂和一个免疫活性剂。α-NaGalase抑制和宏观活性的活动目前正在进行调查。

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.