通过光谱动力学参数研究血卟啉单甲醚与人血清白蛋白的位点结合状况

doi:10.5246/jcps.2013.06.071

中国药学(英文版)

通过光谱动力学参数研究血卟啉单甲醚与人血清白蛋白的位点结合状况

张露勇, 张淼, 邱海霞, 顾瑛^*, 赵井泉^*

1. 中国食品药品检定研究院食品化妆品所, 北京 100050
2. 解放军总医院药品保障中心南楼药房, 北京 100853
3. 解放军总医院激光科, 北京 100853
4. 中国科学院化学研究所, 北京 100190

收稿日期:2013-06-24 修回日期:2013-08-02 出版日期:2013-11-15 发布日期:2014-01-22
通讯作者: 顾瑛*, 赵井泉*

Site- and orientation-specific binding of hematoporphyrin monomethyl ether to human serum albumin revealed by single spectral kinetic parameter

Luyong Zhang, Miao Zhang, Haixia Qiu, Ying Gu^*, Jingquan Zhao^*

1. Institute for Food and Cosmetics Control, National Institutes for Food and Drug Control, Beijing 100050, China
2. Department of Pharmaceutical Care, Chinese PLA General Hospital, Beijing 100853, China
3. Department of Laser Medicine, Chinese PLA General Hospital, Beijing 100853, China
4. Key Laboratory of Photochemistry, Center for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China

Received:2013-06-24 Revised:2013-08-02 Online:2013-11-15 Published:2014-01-22
Contact: Ying Gu*, Jingquan Zhao*

摘要/Abstract

摘要：

通过研究人血清白蛋白的单色氨酸分子 (Trp-214) 或其配合基的荧光响应可以了解人血清白蛋白与药物分子的相互作用机制, 但定性的光谱信息很难得到明确的解释。本实验中, 利用血卟啉单甲醚的环境敏感性和Trp-214基团的荧光响应机制, 研究了血卟啉单甲醚和人血清白蛋白的相互作用。在单一动力参数下, 人血清白蛋白中血卟啉单甲醚的吸光度值与其浓度有线性关系。浓度比为1:1时, 在血卟啉单甲醚的I号结合位点与人血清白蛋白有特异性键连。I号结合位点的微环境类似于在DMSO中。Trp-214的荧光萃灭与血卟啉单甲醚的I号结合位点的吸光度成线性关系说明Trp-214残基的荧光萃灭不是因为能量转移而是因为电子传递。另外相对于竹红菌素B看来, 更容易观察到血卟啉单甲醚或2位氨基牛磺酸替代的竹红菌素与人血清白蛋白的反应, 这归因于生理环境中的静电吸引力。

关键词: 人血浆白蛋白, 光增敏剂, 特异性键连, 维度拟合, 静电驱动

Abstract:

Interaction of a drug molecule with human serum albumin (HSA) is usually studied by fluorescence responses of the ligand or/and the single tryptophan residue (Trp-214) of the protein, but qualitative spectral information may lead to multiple conclusions. In this work, we report a study on the interaction of hematoporphyrin monomethyl ether (HMME) with human serum albumin (HSA), using the environment-sensitive spectra of HMME and reaction-induced fluorescence response of Trp-214. Particularly, the single kinetic parameter, the linear slope, was derived from the concentration-dependent absorbance or fluorescence of HMME in a certain solvent. A quantitative change in the slope at [HMME]/[HSA] = 1:1 clearly demonstrated a specific binding of HMME to site I. The microenvironment in site I may be comparable to that in DMSO solvent, because of the similarity of the slope. Linear correlation of the fluorescence to the absorbance of HMME in site I indicates that the energy transfer is not responsible for Trp-214 fluorescence quenching but an electron transfer may be possible. In addition, much higher rate observed for the binding of HMME or 2-taurine-substituted HB (THB) with HSA than that of hypocrellin B was due to the electrostatic attraction under physiological condition.

Key words: Human serum albumin, Photosensitizing agent, Specific binding, Dimensional fitting, Electrostatic driving

中图分类号:

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Supporting:

Foundation item: National Natural Science Foundation of China (Grant No. 20872144).#br# ^*Corresponding author. Tel.: 86-10-67095914

张露勇, 张淼, 邱海霞, 顾瑛^*, 赵井泉^*. 通过光谱动力学参数研究血卟啉单甲醚与人血清白蛋白的位点结合状况[J]. 中国药学(英文版), DOI: 10.5246/jcps.2013.06.071.

Luyong Zhang, Miao Zhang, Haixia Qiu, Ying Gu^*, Jingquan Zhao^*. Site- and orientation-specific binding of hematoporphyrin monomethyl ether to human serum albumin revealed by single spectral kinetic parameter[J]. Journal of Chinese Pharmaceutical Sciences, DOI: 10.5246/jcps.2013.06.071.

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通过光谱动力学参数研究血卟啉单甲醚与人血清白蛋白的位点结合状况

Site- and orientation-specific binding of hematoporphyrin monomethyl ether to human serum albumin revealed by single spectral kinetic parameter

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