Influence of Low Molecular Weight Salts on the Viscosity of Aqueous-Buffer Bovine Serum Albumin Solutions.
Influence of Low Molecular Weight Salts on the Viscosity of Aqueous-Buffer Bovine Serum Albumin Solutions.
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DOI：
10.3390/molecules27030999
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发表时间：
2022-02-01
期刊：
影响因子：
--
通讯作者：
Lukšič M
中科院分区：
文献类型：
--
作者：
Zdovc B;Jaklin M;Hribar-Lee B;Lukšič M
蛋白质制剂的药物设计旨在最大效率（蛋白质浓度）和最小粘度。因此，了解蛋白质-蛋白质相互作用的性质及其对粘度的影响非常重要。在这项工作中，我们研究了BSA在pH = 4.3的20 mM醋酸盐缓冲液中的粘度对蛋白质浓度和温度（5-45 °C）的依赖性。溶液的粘度随蛋白质浓度增加而增加，并且比160 mg/mL的无蛋白质制剂的粘度高230%。在5至45 °C的温度范围内，粘度降低了几乎60%。修正后的阿克里乌斯理论与实验的一致性是定量的，而硬球模型只提供了实验结果的定性描述。我们还研究了100 mg/mL BSA溶液的粘度作为添加的低分子量盐（LiCl，NaCl，KCl，RbCl，CsCl，NaBr，NaI）的浓度的函数，在盐浓度高达1.75 mol/L的范围内。此外，BSA-盐的混合物的粒度和zeta电位测定的溶液中含有0.5 mol/L的盐。不同阴离子的趋势遵循直接的霍夫迈斯特系列（Cl− > Br− > I−），而对于阳离子，在粘度的情况下观察到间接的霍夫迈斯特系列（Li+ > Na+ > K+ > Rb+ > Cs+），但粒径和zeta电位的值没有显示出阳离子特异性效应。由于蛋白质在pH = 4.3时带正电荷，因此阴离子更多地被吸引到蛋白质表面并屏蔽其电荷，而与阳离子的相互作用不太明显。我们推测，盐表面电荷屏蔽降低蛋白质胶体稳定性，促进蛋白质聚集体的形成。
Pharmaceutical design of protein formulations aims at maximum efficiency (protein concentration) and minimum viscosity. Therefore, it is important to know the nature of protein-protein interactions and their influence on viscosity. In this work, we investigated the dependence of the viscosity of BSA in an aqueous 20 mM acetate buffer at pH = 4.3 on protein concentration and on temperature (5–45 °C). The viscosity of the solution increased with protein concentration and was 230% higher than the viscosity of the protein-free formulation at 160 mg/mL. The viscosity decreased by almost 60% in the temperature range from 5 to 45 °C. The agreement of the modified Arrhenius theory with experiment was quantitative, whereas a hard-sphere model provided only a qualitative description of the experimental results. We also investigated the viscosity of a 100 mg/mL BSA solution as a function of the concentration of added low molecular weight salts (LiCl, NaCl, KCl, RbCl, CsCl, NaBr, NaI) in the range of salt concentrations up to 1.75 mol/L. In addition, the particle size and zeta potential of BSA-salt mixtures were determined for solutions containing 0.5 mol/L salt. The trends with respect to the different anions followed a direct Hofmeister series (Cl− > Br− > I−), whereas for cations in the case of viscosity the indirect Hofmeister series was observed (Li+ > Na+ > K+ > Rb+ > Cs+), but the values of particle sizes and zeta potential did not show cation-specific effects. Since the protein is positively charged at pH = 4.3, anions are more attracted to the protein surface and shield its charge, while the interaction with cations is less pronounced. We hypothesize that salt surface charge shielding reduces protein colloidal stability and promotes protein aggregate formation.
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DOI：
10.1016/0141-8130(95)01057-2
发表时间：
1996-02-01
影响因子：
8.2
作者：
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通讯作者：
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影响因子：
3.3
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DOI：
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发表时间：
1991-09-01
影响因子：
3.2
作者：
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影响因子：
6
作者：
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影响因子：
2.9
作者：
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