Tanaka T, Kaneo Y, Miyashita M
Department of Biopharmaceutics, School of Pharmacy, Fukuyama University, Japan.
Biol Pharm Bull. 1996 May;19(5):774-7. doi: 10.1248/bpb.19.774.
Macromolecular conjugates of mitomycin C (MMC) were synthesized by binding an active ester of glutarylated MMC (MMC-G-OSu) to human holo-transferrin (TF). Water-soluble TF-MMC conjugates (TF-G-MMC) were obtained in a good yield (> 95%) by this method. The MMC content of the conjugate increased (0.82-9.49 MMC/w%) with increasing amounts of MMC-G-OSu added to the conjugation mixture. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed no aggregation in these conjugates. 125I-TF-G-MMC was bound specifically to the TF receptor on Sarcoma 180 cells; the measurement of equilibrium binding of the 125I-labeled conjugate resulted in a saturation isotherm. The amount of conjugate specifically bound to the TF receptor decreased as the MMC content of the conjugate increased. However, it was found that the conjugate with an MMC content below 10 mol MMC/mol TF still retains a binding activity of more than half that of TF. Therefore, when an optimal chemical modification was chosen, TF could be used as a tumor specific drug carrier.
通过将戊二酰化丝裂霉素C（MMC-G-OSu）的活性酯与人类全转铁蛋白（TF）结合，合成了丝裂霉素C（MMC）的大分子缀合物。通过该方法以高收率（>95%）获得了水溶性TF-MMC缀合物（TF-G-MMC）。随着添加到缀合混合物中的MMC-G-OSu量的增加，缀合物的MMC含量增加（0.82 - 9.49 MMC/w%）。十二烷基硫酸钠 - 聚丙烯酰胺凝胶电泳（SDS-PAGE）分析表明这些缀合物中没有聚集现象。125I-TF-G-MMC特异性结合于肉瘤180细胞上的TF受体；对125I标记的缀合物平衡结合的测量产生了饱和等温线。随着缀合物中MMC含量的增加，特异性结合到TF受体上的缀合物量减少。然而，发现MMC含量低于10 mol MMC/mol TF的缀合物仍保留超过TF一半的结合活性。因此，当选择最佳化学修饰时，TF可用作肿瘤特异性药物载体。
