金-199通过巯基苹果酸标记丙种球蛋白的化学研究

Chemical Study on Labelling of γ-Globulin with ^(199)Au via Thiomalic Acid

^(199)Au标记的抗肿瘤单克隆抗体,适用于肿瘤的诊断和治疗。本工作采用人丙种球蛋白(IgG)作为单抗的模型蛋白质,巯基苹果酸(TMA)为连接IgG与Au的双功能连接剂。系统地研究了S-乙酰巯基琥珀酸酐(AMSA)的制备、AMSA与IgG的偶连、水解出巯基,以及IgG-TMA偶连体与Au的化学反应条件和影响因素。用此法所得标记化合物^(199)Au-TMA-IgG在空气中不够稳定,在体内的稳定性有待进一步考查。所得结果可推广用于标记单克隆抗体。

199Au-labelled monoclonal antibody against cancer may be applied to the diagnosis and therapy of tumors. In this study, γ-globulin (IgG) was used as the protein model of monoclonal antibody, and thiomalic acid (TMA) as the bifunctional conjugate connecting gold to IgG. We have systematically studied the preparation of S-acetylmercap-tosuccinic anhydride (AMSA), the conjugation of IgG with AMSA, the release of thiols from AMSA conjugating IgG by hydrolysis, and the reaction condition of the conjugate IgG-TMA with gold. However, the labelled compound Au-TMA-IgG, is not very stable in air, and it needs further study to verify whether the label is stable in vivo or not. The result obtained could be applied to the labelling of monoc-lonal antibody.