抗癌铂（IV）配合物的结构及细胞摄入的动力学和机制的研究

目的 分析抗癌铂(Ⅳ)配合物的结构，研究人红细胞摄入这些配合物的动力学和机制.方法 利用分子图形模拟方法计算5种口服抗癌铂(Ⅳ)配合物的结构；利用动力学方法测定细胞摄入配合物的速率常数；根据细胞膜蛋白巯基含量和内源性荧光的改变，探讨这些铂(Ⅳ)配合物与人红细胞的作用。结果 计算出了5种口服抗癌铂(Ⅳ)配合物的结构；得到了细胞摄入配合物的一级动力学常数；配合物与细胞膜作用过程中，膜蛋白巯基含量变化很小，但膜蛋白的内源性荧光发生了改变.结论 人红细胞摄入4个铂(Ⅳ)配合物服从简单扩散的一级动力学过程，速率常数不同，细胞摄入配合物(JM221)不符合一级动力学过程。配合物与细胞膜作用使膜蛋白的构象发生了变化，与膜蛋白和膜脂发生了较弱的作用.

Studies on the structures of Pt (IV) anticancer complexes and the kinetics and mechanism of their cellular up-take

OBJECTIVE To analyze the optimal structures of five Pt (IV) anticancer complexes, and study the kinetics and mechanism of the uptake of these complexes by human erythrocytes. METHODS The optimal structures of five Pt (IV) anticancer complexes were calculated using simulation method of molecular modeling. The first-order rate constants of their cellular uptake were measured. The interaction of the complexes with human erythrocytes was discussed based on the change of mercapto-groups contents in membrane proteins and intrinsic fluorescence of membrane proteins. RESULTS These complexes entered human erythrocytes by way of simple passive diffusion, and the first-order rate constants of their cellular uptake were obtained. There were a litter change of mercapto-groups contents in membrane proteins in the process of interaction of the complexes with human erythrocytes membrane, but the intrinsic fluorescence of membrane proteins was changed. CONCLUSION Four complexes entered human erythrocytes by process of first-order kinetics of simple passive diffusion, but their rate constants are not same. The uptake process of the complex JM221 by the human erythrocytes does not follow first-order kinetics. The conformation changes of membrane proteins may have occurred due to the weak interaction of the complexes with membrane.