Schott H, Leitner B, Schwendener R A, Hengartner H
Institut für Organische Chemie, Universität Tübingen, F.R.G.
J Chromatogr. 1988 May 27;441(1):115-24. doi: 10.1016/s0021-9673(01)84659-8.
The antitumour drug 1-beta-D-arabinofuranosylcytosine (ara C) was acylated by means of oleic acid anhydride, resulting in the prodrug N4-oleoyl-ara C. Together with a lipophilic biotin derivative, this lipophilic prodrug was incorporated into the bilayer membrane of unilamellar liposomes prepared by means of the detergent dialysis method. On addition of these biotinylated prodrug-liposomes to an excess of avidin, biotin residues were complexed with avidin. The unreacted avidin was removed by chromatography on the Ultrogel AcA-22 column. The prodrug-liposome-avidin complex was coupled to biotinylated monoclonal antibodies through the free binding sites of the immobilized avidin. Unreacted antibodies were removed by chromatography on an Ultrogel AcA-22 column. In vitro, the liposome-antibody complexes selectively bound to cells which were recognized by the monoclonal antibodies linked to the liposomes. For this reason, a promising strategy towards a specific chemotherapy of cancer is expected.
抗肿瘤药物1-β-D-阿拉伯呋喃糖基胞嘧啶（阿糖胞苷，ara C）通过油酸酐进行酰化，生成前药N4-油酰基-阿糖胞苷。该亲脂性前药与亲脂性生物素衍生物一起，通过去污剂透析法制备的单层脂质体双层膜中。将这些生物素化的前药脂质体加入过量的抗生物素蛋白中，生物素残基与抗生物素蛋白形成复合物。未反应的抗生物素蛋白通过在Ultrogel AcA-22柱上进行色谱分离去除。前药脂质体-抗生物素蛋白复合物通过固定化抗生物素蛋白的游离结合位点与生物素化单克隆抗体偶联。未反应的抗体通过在Ultrogel AcA-22柱上进行色谱分离去除。在体外，脂质体-抗体复合物选择性地结合到与脂质体连接的单克隆抗体所识别的细胞上。因此，有望实现一种针对癌症的特异性化疗策略。
