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978-3-8439-2494-8, Reihe Thermodynamik

Marcel Herhut
Thermodynamic Modeling of Protein Solubility in Aqueous Polymer/Salt Solutions (Band 17)

112 Seiten, Dissertation Technische Universität Dortmund (2015), Softcover, A5

Zusammenfassung / Abstract

Within the last decades Biopharmaceuticals, especially pharmaceutical proteins, have gained an increased influence in worldwide revenue in red biotechnology. The production of pharmaceutical proteins is very expensive, since state-of-the-art protein-purification by a series of chromatographic steps is very cost intensive. An alternative to the common purification processes is the aqueous-two-phase extraction, crystallization and precipitation of proteins. These processes were avoided in the past, since protein solubility is crucial information for developing them. Unfortunately, the experimental effort to estimate the protein solubility is very high.

In this work the sol-xDLVO model was developed to predict protein solubility in aqueous salt solutions as function of temperature, pH and salt concentration. For this the second osmotic virial coefficient and the protein solubility was measured for lysozyme, γ-globulin from human blood, D-xylose ketol-isomerase and a monoclonal antibody in aqueous salt solutions. Within the measurements temperature, pH and salt concentration were varied in order to consider the significant influences on second osmotic virial coefficient and protein solubility. The sol-xDLVO model was then used to model and predict the second osmotic virial coefficient and protein-solubility data. The results were in good agreement with the experimental data.

In the next step the sol-xDLVO model was modified using the mPRISM potential to form the sol-mxDLVO model, since the sol-xDLVO model is limited to aqueous salt solutions. Compared to the sol-xDLVO model the sol-mxDLVO model can consider the influence of hydrophilic polymers on protein solubility. For this the second osmotic virial coefficient and the protein solubility was measured for lysozyme, γ-globulin from human blood and D-xylose ketol-isomerase in aqueous polymer-salt solutions. The sol-mxDLVO model predicted the protein solubility for these systems in good agreement with the experimental data.

The results of this work show that the experimental effort for measuring protein solubility can be decreased by using the sol-mxDLVO model. This leads to an accelerated development of aqueous-two-phase extraction, crystallization and precipitation processes for proteins.