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溶酶体靶向表面活性剂与牛血清白蛋白之间生物分子相互作用的物理化学研究。

Physicochemical study of biomolecular interactions between lysosomotropic surfactants and bovine serum albumin.

机构信息

Department of Inorganic Chemistry, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211a, 50-556, Wroclaw, Poland.

Department of Inorganic Chemistry, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211a, 50-556, Wroclaw, Poland.

出版信息

Colloids Surf B Biointerfaces. 2017 Nov 1;159:750-758. doi: 10.1016/j.colsurfb.2017.08.046. Epub 2017 Aug 30.

DOI:10.1016/j.colsurfb.2017.08.046
PMID:28886512
Abstract

The interactions between two cationic lysosomotropic surfactants (2-dodecanoyloxyethyl)trimethylammonium bromide (DMM-11) and (2-dodecanoyloxypropyl)trimethylammonium bromide (DMPM-11) with bovine serum albumin (BSA) in Hepes buffer (pH=7.4) were systematically studied by surface tension, fluorescence and circular dichroism (CD) spectroscopy and isothermal titration calorimetry (ITC). Furthermore, the size of the micellar aggregates and the polydispersity indexes of both cationic surfactants were studied by dynamic light scattering technique (DLS). The hydrodynamic radii, micellar volumes and aggregation numbers were calculated using a method based on density functional theory (DFT). The results showed that, in both cases, the surface tension was modified upon addition of BSA, and the critical micelle concentration (CMC) values of DMM-11 and DMPM-11 were higher in the presence of BSA. The fluorescence intensity of BSA decreased significantly as the concentration of both cationic surfactants increased and this effect was attributed to the formation of surfactant-BSA complexes. Synchronous fluorescence spectrometry showed the binding-induced conformational changes in BSA. Finally, CD and DLS results revealed the occurrence of changes in the secondary structure of the protein in the presence of both surfactants. In conclusion, understanding the interactions between lysosomotropic surfactants and BSA is required to explore their potential applications in medicine.

摘要

两种阳离子溶酶体表面活性剂(2-十二烷氧乙基)三甲基溴化铵(DMM-11)和(2-十二烷氧丙基)三甲基溴化铵(DMPM-11)与牛血清白蛋白(BSA)在 Hepes 缓冲液(pH=7.4)中的相互作用通过表面张力、荧光和圆二色性(CD)光谱以及等温热力学滴定(ITC)进行了系统研究。此外,还通过动态光散射技术(DLS)研究了两种阳离子表面活性剂的胶束聚集物的大小和多分散指数。使用基于密度泛函理论(DFT)的方法计算了水动力半径、胶束体积和聚集数。结果表明,在这两种情况下,BSA 的加入都会改变表面张力,并且在存在 BSA 的情况下,DMM-11 和 DMPM-11 的临界胶束浓度(CMC)值更高。随着两种阳离子表面活性剂浓度的增加,BSA 的荧光强度显著降低,这归因于形成了表面活性剂-BSA 配合物。同步荧光光谱表明 BSA 的结合诱导了构象变化。最后,CD 和 DLS 结果表明,在两种表面活性剂存在的情况下,蛋白质的二级结构发生了变化。总之,为了探索溶酶体表面活性剂在医学中的潜在应用,需要了解它们与 BSA 之间的相互作用。

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