...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Biomolecular Structure and Dynamics >Exploring the combination characteristics of lumefantrine, an antimalarial drug and human serum albumin through spectroscopic and molecular docking studies
【24h】

Exploring the combination characteristics of lumefantrine, an antimalarial drug and human serum albumin through spectroscopic and molecular docking studies

机译：通过光谱和分子对接研究探索Lumefantrine，抗疟药和人血清白蛋白的组合特征

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Binding of lumefantrine (LUM), an antimalarial drug to human serum albumin (HSA), the main carrier protein in human blood circulation was investigated using fluorescence quenching titration, UV-vis absorption and circular dichroism (CD) spectroscopy as well as molecular docking. LUM-induced quenching of the protein (HSA) fluorescence was characterized as static quenching, as revealed by the decrease in the value of the Stern-Volmer quenching constant, K-sv with increasing temperature, thus suggesting LUM-HSA complex formation. This was also confirmed from the UV-vis absorption spectral results. Values of the association constant, K-a for LUM-HSA interaction were found to be within the range, 7.27-5.01 x 10(4) M-1 at three different temperatures, i.e. 288 K, 298 K and 308 K, which indicated moderate binding affinity between LUM and HSA. The LUM-HSA complex was stabilized by hydrophobic interactions, H-bonds, as well as van der Waals forces, as predicted from the thermodynamic data (Delta S = +50.34 J mol(-1) K-1 and Delta H = -12.3 kJ mol(-1)) of the binding reaction. Far-UV and near-UV CD spectral results demonstrated smaller changes in both secondary and tertiary structures of HSA upon LUM binding, while three-dimensional fluorescence spectra suggested alterations in the microenvironment around protein fluorophores (Trp and Tyr). LUM binding to HSA offered stability to the protein against thermal stress. Competitive drug displacement results designated Sudlow's Site I, located in subdomain IIA of HSA as the preferred binding site of LUM on HSA, which was well supported by molecular docking analysis.
机译：采用荧光猝灭滴定、紫外-可见吸收光谱、圆二色谱（CD）光谱以及分子对接技术，研究了抗疟药物lumefantrine（LUM）与人体血液循环中主要载体蛋白人血清白蛋白（HSA）的结合。LUM诱导的蛋白质（HSA）荧光猝灭表现为静态猝灭，这一点可以通过Stern-Volmer猝灭常数K-sv值随温度升高而降低来揭示，从而表明LUM-HSA复合物的形成。紫外-可见吸收光谱结果也证实了这一点。研究发现，在288 K、298 K和308 K三种不同温度下，LUM-HSA相互作用的结合常数K-a的值在7.27-5.01 x 10（4）M-1范围内，这表明LUM和HSA之间具有中等的结合亲和力。根据结合反应的热力学数据（δS=+50.34 J mol（-1）K-1和δH=-12.3 kJ mol（-1））预测，LUM-HSA复合物通过疏水作用、氢键以及范德华力稳定。远紫外和近紫外CD光谱结果表明，LUM结合后，HSA的二级和三级结构都发生了较小的变化，而三维荧光光谱表明蛋白质荧光团（Trp和Tyr）周围的微环境发生了改变。LUM与HSA的结合为蛋白质提供了抵抗热应激的稳定性。竞争性药物置换结果将位于HSA亚结构域IIA中的Sudlow位点I指定为LUM在HSA上的首选结合位点，这一点得到了分子对接分析的充分支持。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号