Prediction and characterization of the stability enhancing effect of the Cherry-Tag ™ in highly concentrated protein solutions by complex rheological measurements and MD simulations

Publication date: 5 October 2017 Source:International Journal of Pharmaceutics, Volume 531, Issue 1 Author(s): Pascal Baumann, Marie-Therese Schermeyer, Hannah Burghardt, Cathrin Dürr, Jonas Gärtner, Jürgen Hubbuch Solution stability attributes are one of the key parameters within the production and launching phase of new biopharmaceuticals. Instabilities of active biological compounds can reduce the yield of biopharmaceutical productions, and may induce undesired reactions in patients, such as immunogenic rejections. Protein solution stability thus needs to be engineered and monitored throughout production and storage. In contrast to the gold standard of long-term storage experiments applied in industry, novel experimental and in silico molecular dynamics tools for predicting protein solution stability can be applied within several minutes or hours. Here, a rheological approach in combination with molecular dynamics simulations are presented, for determining and predicting long-term phase behavior of highly concentrated protein solutions. A diversity of liquid phase conditions, including salt type, ionic strength, pH and protein concentration are tested in a Glutathione-S-Transferase (GST) case study, in combination with the enzyme with and without solubility-enhancing Cherry-Tag™. The rheological characterization of GST and Cherry-GST solutions enabled a fast and efficient prediction of protein instabilities without the need of long-term protein phase diagrams....
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research