Inclusion of mPRISM potential for polymer‐induced protein interactions enables modeling of second osmotic virial coefficients in aqueous polymer‐salt solutions. Issue 1 (24th September 2015)

• Record Type: Journal Article
• Authors: Herhut, Marcel; Brandenbusch, Christoph; Sadowski, Gabriele
• Is Part Of: Biotechnology journal. Volume 11:Issue 1(2016)
• Page Start: 146
• Page End: 154
• Publication Date: 2015-09-24
• Subjects: Modeling second osmotic virial coefficient -- Polymer influence on proteins -- Protein‐protein interactions -- Protein solubility; Biotechnology -- Periodicals; 660.605
• DOI: 10.1002/biot.201500086
• Languages: English
• ISSNs: 1860-6768

Abstract

Abstract: The downstream processing of therapeutic proteins is a challenging task. Key information needed to estimate applicable workup strategies (e.g. crystallization) are the interactions of the proteins with other components in solution. This information can be deduced from the second osmotic virial coefficient B 22, measurable by static light scattering. Thermodynamic models are very valuable for predicting B 22 data for different process conditions and thus decrease the experimental effort. Available B 22 models consider aqueous salt solutions but fail for the prediction of B 22 if an additional polymer is present in solution. This is due to the fact that depending on the polymer concentration protein‐protein interactions are not rectified as assumed within these models. In this work, we developed an extension of the xDLVO model to predict B 22 data of proteins in aqueous polymer‐salt solutions. To show the broad applicability of the model, lysozyme, γ‐globulin and D‐xylose ketol isomerase in aqueous salt solution containing polyethylene glycol were considered. For all proteins considered, the modified xDLVO model was able to predict the experimentally observed non‐monotonical course in B 22 data with high accuracy. When used in an early stage in process development, the model will contribute to an efficient and cost effective downstream processing development. Abstract : The addition of polymers induce complex protein‐protein interactions in aqueous solution. At low concentration, polymers are present as coils (A), leading to induced attractive interactions between protein molecules (P); at high concentration, polymers are present as chains (B), inducing repulsive interactions between protein molecules. Accounting for the concentration effect enables the simulation of non‐monotonic solubility behavior of proteins in the presence of polymers such as polyethylene glycol (PEG).