Wunderlich G, Schwarz U, Franke W G, Brossmer R
Medizinische Akademie Dresden, Klinik und Poliklinik für Nuklearmedizin, Germany.
J Nucl Biol Med (1991). 1994 Dec;38(4 Suppl 1):15-7.
There are various approaches for improving endoradiotherapy and diagnosis with monoclonal antibodies in nuclear medicine. The known methods of site-specific labelling of biomolecules based either on reactions with sulfhydryl groups or on reactions with aldehyde groups of the oligosaccharide chains effect unwanted alterations of the biomolecules. We present a new method to introduce radioactive halogens into the oligosaccharide chains of an antibody, based on the enzymatic transfer of the labelled synthetic sialic acid derivative CMP-9-deoxy-9-salizoyl-NeuAc. It was first labelled by the iodogen-method (iodine) in yields of more than 90%. Under selected conditions it was possible to obtain di- and trihalogenated products. Then the radioactive sialic acid derivatives were transferred during 90 minutes at room temperature with 2.6-sialyltransferase from rat liver into the oligosaccharide chains of antibodies. It is necessary to use neuraminidase pretreated antibodies with an increased number of binding sites for sialic acid derivatives. Yields of about 55% were obtained for the monoiodinated sialic acid derivative. With this method we present a reasonable alternative reaction of labelled compounds with biomolecules. Studies of the immunoreactivity are now in progress.
在核医学中，有多种方法可用于改进单克隆抗体的放射治疗和诊断。已知的基于与巯基反应或与寡糖链醛基反应的生物分子位点特异性标记方法会对生物分子产生不必要的改变。我们提出了一种基于标记的合成唾液酸衍生物CMP-9-脱氧-9-水杨酰基神经氨酸的酶促转移，将放射性卤素引入抗体寡糖链的新方法。它首先通过碘代法（碘）标记，产率超过90%。在选定条件下，可以获得二卤代和三卤代产物。然后在室温下，用大鼠肝脏的2.6-唾液酸转移酶在90分钟内将放射性唾液酸衍生物转移到抗体的寡糖链中。有必要使用对唾液酸衍生物结合位点数量增加的神经氨酸酶预处理抗体。单碘化唾液酸衍生物的产率约为55%。通过这种方法，我们提出了一种标记化合物与生物分子的合理替代反应。免疫反应性的研究正在进行中。
