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首页> 外文期刊>Biophysical Chemistry: An International Journal Devoted to the Physical Chemistry of Biological Phenomena >A thermodynamic analysis of the binding interaction between polysorbate 20 and 80 with human serum albumins and immunoglobulins: a contribution to understand colloidal protein stabilisation.
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A thermodynamic analysis of the binding interaction between polysorbate 20 and 80 with human serum albumins and immunoglobulins: a contribution to understand colloidal protein stabilisation.

机译：聚山梨酯20和80与人血清白蛋白和免疫球蛋白之间的结合相互作用的热力学分析：有助于了解胶体蛋白的稳定性。

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摘要

The development of liquid therapeutic protein drugs imposes the presence of specific stabilisation agents to prevent protein degradation in order to reach shelf-lives of at least 2 years for drugs stored at 2-8 degrees C. Non-ionic detergents are used to avoid protein adsorption and the formation of protein aggregates. Depending on the protein and excipient (detergent) used the stabilisation effect is quite different and cannot be predicted up to now. One reason for this is the inadequate understanding of the principles that govern the stabilisation of proteins in the presence of detergents. One stabilisation mechanism discussed implicates a direct binding of detergent molecules to the hydrophobic surface area(s) of the protein in order to minimise protein-protein interactions and thus protein aggregation. Therefore, the presented study considers the interaction and binding of polysorbate 20 and 80 to various human serum albumins and immunoglobulins of different subtypes. The interaction is analysed by means of isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC). From ITC the binding constant is derived as well as the thermodynamic parameters. The thermal protein stability is obtained from DSC. The results show that binding of the two detergents to human serum albumin is observed with binding constants of approximately approximately 10(3) M(-1), with 1-3 detergent molecules binding to the albumins. The exact polysorbate-albumin ratio depends on the used albumin fraction. The interaction of the detergent is also obvious from the DSC results, showing an increase of the denaturation temperature. However, the binding of the detergent to the three investigated immunoglobulins is quite low and negligible, thus showing that for immunoglobulins a direct and strong polysorbate binding to the protein is not the reason for the colloidal stabilisation effect of immunoglobulins in solution in the presence of polysorbate 20 or 80.
机译：液体治疗性蛋白质药物的发展要求存在特定的稳定剂，以防止蛋白质降解，以使在2-8摄氏度下储存的药物至少达到2年的保质期。使用非离子型去污剂来避免蛋白质吸附和蛋白质聚集体的形成。根据所使用的蛋白质和赋形剂（洗涤剂）的不同，稳定作用也大不相同，目前尚无法预测。原因之一是对在去污剂存在下控制蛋白质稳定的原理的理解不足。所讨论的一种稳定机制涉及去污剂分子与蛋白质的疏水表面积的直接结合，以使蛋白质与蛋白质的相互作用以及蛋白质的聚集最小化。因此，本研究考虑了聚山梨酯20和80与各种人血清白蛋白和不同亚型的免疫球蛋白的相互作用和结合。通过等温滴定热法（ITC）和差示扫描量热法（DSC）分析相互作用。从ITC导出结合常数以及热力学参数。热蛋白质稳定性从DSC获得。结果表明，观察到两种去污剂与人血清白蛋白的结合，结合常数约为10（3）M（-1），1-3个去污剂分子与白蛋白结合。确切的聚山梨酯-白蛋白比率取决于所用的白蛋白分数。从DSC结果也可明显看出去污剂的相互作用，表明变性温度的升高。然而，去污剂与三种研究的免疫球蛋白的结合非常低且可忽略不计，因此表明对于免疫球蛋白而言，直接和强力的聚山梨酯与蛋白质的结合并不是免疫球蛋白在溶液中存在聚山梨酯时胶体稳定作用的原因。 20或80。

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