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抗癌Pt(II)络合物与人红细胞收缩蛋白的相互作用

杨晓改, 李荣昌   

  1. 北京医科大学生物无机及无机药物化学系, 北京 100083
  • 收稿日期:1997-10-13 修回日期:1998-04-17 出版日期:1998-09-15 发布日期:1998-09-15

Interactions Between Anticancer Pt(II) complexes and Human Erythrocyte Spectrin

Xiao-Gai Yang, Rong-Chang Li   

  1. Department of Bioinorganic and Inorganic Pharmaceutical Chemistry, Beijing Medical University, Beijing 100083
  • Received:1997-10-13 Revised:1998-04-17 Online:1998-09-15 Published:1998-09-15

摘要: 用荧光及园二色谱对人红细胞收缩蛋白(SP)与不同组成和构型的Pt(I)络合物的作用进行了研究。结果表明, SP4.7×102个顺铂(CDDP)结合部位。其中, 最高亲和性部位70, K1>3.47×106; 较高亲和性的1.8×102, K2 = 3.47×106; 其余2.2×102个为低亲和性的, K3 = 8.77×105Pt(II)络合物与SP的结合导致SP构象变化, 这种变化与Pt(II)络合物浓度及络合物与SP的浓度比有关。CDDP及顺式二水二氨合铂(II)SP的作用在初始1 h内遵从双阶段一级动力学, 动力学常数也已测定。反应1 h, 为络合物与SP作用的后续变化阶段, 这一阶段可能涉及SP的构象改变、聚合及解聚。值得注意的是, SP1, 2-环己二胺不同异构体作为载体配体的Pt(II)络合物作用时, 空间匹配性比Pt(II)SP的巯基的亲和性显得更为重要。

关键词: : Pt(II)络合物, 收缩蛋白, 构象, 结合部位, 动力学, 手性

Abstract: The interactions between human erythrocyte spectrin(SP) and Pt(II) complexes with different composition and configuration were studied by fluorescence and circular dichroism spectra. The results showed that there are 4.7×102 binding sites of cisplatin(CDDP) in a spectrin tetramer(SPT). Among them, about 70 sites with apparent binding constant K1>3.47×106 were of highest affinity, 1.8×102 sites with K2 = 3.47×106 were of high affinity, and other 2.2×102 sites with K3 = 8.77×105 were of low affinity. The conformation change of spectrin, depending on the concentration of Pt(II) complex and molar ratio (R) of Pt(II) complex to spectrin, was induced by the binding of Pt(II) complexes. It indicated that the interaction of both CDDP and cis-diaquodiamine platinum (DADP) with SP followed a twostep first order kinetic process in the first stage (1 h), and the kinetic constants were determined. In the second stage, the induced conformation change, polymerization and depolymerization of SP were probably involved. It was noticed that in the reaction of SP and Pt(II) complexes with 1,2-cyclohexanediammine isomers as chiral carrier ligand, stereo-matching played a more important role than the affinity of Pt(II) to thiol groups of SP.

Key words: Pt(II) complex, Spectrin, Conformation, Binding sites, Kinetic, Chiral

Supporting: *This subject was supported by National Natural Science Foundation of China.