人血清白蛋白与硫代寡核苷酸的结合研究

人血清白蛋白与硫代寡核苷酸的结合研究

叶国柱, 张亮仁^*, 张礼和

北京大学药学院天然药物及仿生药物国家重点实验室, 北京 100083

收稿日期:2006-11-10 修回日期:2007-02-10 出版日期:2007-03-15 发布日期:2007-03-15
通讯作者: 张亮仁*

Investigation of the binding behavior of human serum albumin and phosphorothioate oligodeoxynucleotide

Guo-Zhu Ye, Liang-Ren Zhang^*, Li-He Zhang

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China

Received:2006-11-10 Revised:2007-02-10 Online:2007-03-15 Published:2007-03-15
Contact: Liang-Ren Zhang*

摘要/Abstract

摘要： 目的研究二价阳离子对白蛋白与硫代寡核苷酸结合的影响以及结合硫代寡核苷酸后白蛋白构象的改变。方法应用表面等离子体共振、圆二色散以及荧光光谱法对白蛋白与硫代寡核苷酸的结合行为进行了表征。结果 (1)随着pH值升高,结合能力降低; (2)锌离子能显著促进白蛋白与硫代寡核苷酸的结合, 镍离子也促进结合, 但与锌离子相比作用稍弱; (3)与硫代寡核苷酸结合后, 白蛋白结构发生变化, 产生β-折叠构造。结论通过实验方法证明硫代寡核苷酸结合于白蛋白的正电荷密集区; 表明白蛋白可能介导硫代寡核苷酸的胞吞行为。

关键词: 硫代寡核苷酸, 硫代寡核苷酸, 硫代寡核苷酸, 白蛋白, 白蛋白, 白蛋白, 正电荷密集区, 正电荷密集区, 正电荷密集区, 构象变化, 构象变化, 构象变化

Abstract: Aim To study the binding behavior between human serum albumin(HSA) and phosphorothioate oligodeoxynucleotide(PS-ODN) and the effects of bivalent cations on the interaction. Methods Surface plasma resonance, circular dichroism and fluorescence experiments were conducted. Results (1) the binding ability was decreased along with the increase of pH; (2) Zn²⁺ and Ni²⁺ enhanced the interaction between PS-ODN and HSA; (3) Upon PS-ODN binding, the conformation of HSA was changed with an increase of β-sheet. Conclusion The results provide experimental evidences to the hypothesis that PS-ODN binds with HSA in the positive potential region, and histidine residues located in the region play a crucial role in the interaction.

Key words: Phosphorothioate oligodeoxynucleotide, Phosphorothioate oligodeoxynucleotide, Human serum albumin, Human serum albumin, Positive potential region, Positive potential region, Conformational changes, Conformational changes

中图分类号:

R913
R916.2

Supporting:

^*Corresponding author. Tel.: 86-10-82802567; fax: 86-10-82802724

叶国柱, 张亮仁^*, 张礼和. 人血清白蛋白与硫代寡核苷酸的结合研究[J]. .

Guo-Zhu Ye, Liang-Ren Zhang^*, Li-He Zhang . Investigation of the binding behavior of human serum albumin and phosphorothioate oligodeoxynucleotide[J]. .

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