高等学校化学学报

高等学校化学学报 ›› 2009, Vol. 30 ›› Issue (7): 1314.

• 研究论文 • 上一篇    下一篇

氯硝柳胺及其衍生物与钥孔戚血蓝蛋白的相互作用

郭维, 吴勇权, 郑绿茵, 许丽荣, 范小林   

  1. 赣南师范学院, 江西省有机药物化学重点实验室, 赣州 341000
  • 收稿日期:2008-10-07 出版日期:2009-07-10 发布日期:2009-07-10
  • 通讯作者: 范小林, 男, 博士, 教授, 主要从事血吸虫防治新技术和新药物研究. E-mail: vanxl@gnnu.edu.cn
  • 基金资助:

    国家自然科学基金(批准号: 50478117)、2006年江西省科技厅重大招标计划、江西省自然科学基金(批准号: 2007GQH0366)和江西省教育厅科技计划项目(批准号: GJJ08385)资助.

Interaction of Keyhole Limpet Hemocyanin with Niclosamide and Its Derivative

GUO Wei, WU Yong-Quan, ZHENG Lü-Yin, XU Li-Rong, FAN Xiao-Lin*   

  1. Key Laboratory of Organo-pharmaceutical Chemistry of Jiangxi Province, Gannan Normal University, Ganzhou 341000, China
  • Received:2008-10-07 Online:2009-07-10 Published:2009-07-10
  • Contact: FAN Xiao-Lin. E-mail: vanxl@gnnu.edu.cn
  • Supported by:

    国家自然科学基金(批准号: 50478117)、2006年江西省科技厅重大招标计划、江西省自然科学基金(批准号: 2007GQH0366)和江西省教育厅科技计划项目(批准号: GJJ08385)资助.

PDF (PC)

被引次数

9

摘要：

以氯硝柳胺为原料合成了聚乙二醇200基氯硝柳胺. 采用荧光光谱、同步荧光光谱、紫外吸收光谱和圆二色谱研究了氯硝柳胺及其衍生物与钥孔戚血蓝蛋白(KLH)的相互作用. 结果表明, 两种药物分子对KLH的荧光猝灭机制属于静态猝灭; 由Lineweaver-Burk方程计算出不同温度下结合常数K, 但是聚乙二醇200基氯硝柳胺与KLH的作用相对较弱; 由Van′t Hoff方程计算出ΔH和ΔS平均值, 结合力主要为静电作用力; 热力学函数计算结果表明, 氯硝柳胺及其衍生物与KLH的作用过程是一个熵增加、Gibbs自由能降低的自发分子间作用过程; 根据Förster非辐射能量转移机制求得给体与受体间的结合距离r均小于7 nm; 同步荧光光谱表明, 氯硝柳胺及其衍生物能够被血蓝蛋白存储和转运, 但结合时对蛋白构象有一定影响; 圆二色谱测得加入两种药物后, KLH的α-螺旋含量均降低, 二级结构发生改变. 通过比较氯硝柳胺及其衍生物与KLH的相互作用, 初步探讨了分子结构与其结合能力之间的联系.

关键词: 钥孔戚血蓝蛋白; 紫外吸收光谱; 荧光光谱; 同步荧光光谱; 圆二色谱

Abstract:

PEG200-niclosamide was obtained from niclosamide. The interaction between keyhole limpet hemocyanin(KLH) and niclosamide/PEG200-niclosamide was investigated by fluorescence spectra, synchronous fluorescence spectra, ultraviolet absorption spectra and circular dichroism(CD) spectra. It was shown that KLH fluorescence at 340 nm was quenched regularly with the addition of niclosamide/PEG200-niclosamide; the quenching constant decreased as temperature increased; and the quenching mechanism with KLH was suggested as a static fluorescence quenching process. The binding constants(K) were obtained respectively according to Lineweaver-Burk equation at different temperatures, while there was a weaker interaction of the PEG200-niclosamide with KLH than that with niclosamide. The calculated thermodynamic parameters(ΔH, ΔS) by Van′t Hoff equation indicated that the electrostatic interaction played major roles in the binding processes. The binding processes of KLH with niclosamide/PEG200-niclosamide were spontaneous inter-molecular interaction in which entropy increased and Gibbs free energy decreased. The distances between KLH and niclosamide/PEG200-niclosamide were less than 7 nm according to the theory of the Frster energy transference. The effects of niclosamide and PEG200-niclosamide on the conformation of KLH were further analyzed by synchronous fluorescence spectra and circular dichroism spectra. Both niclosamide and PEG200-niclosamide could be deposited and transported by KLH and they affected the conformation of KLH. The CD spectra proved that the α-helix contents of KLH decreased, and the relative contents of secondary structure units of KLH changed in these binding processes. The relationship between the molecule structures and their binding ability was discussed preliminarily by comparison of the interactions between KLH and niclosamide/PEG200-niclosamide..

Key words: Keyhole limpet hemocyanin; Ultraviolet spectroscopy; Fluorescence spectroscopy; Synchronous fluorescence spectroscopy; Circular dichroism spectrometry

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