Addition of sodium malonate alters the morphology and increases the critical flux during tangential flow filtration of precipitated immunoglobulins
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2024
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| _version_ | 1867021538677489664 |
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| author | Ali Behboudi Mirko Minervini Zachary S. Badinger William W. Haddad Andrew L. Zydney |
| author_facet | Ali Behboudi Mirko Minervini Zachary S. Badinger William W. Haddad Andrew L. Zydney Ali Behboudi Mirko Minervini Zachary S. Badinger William W. Haddad Andrew L. Zydney |
| collection | Wiley Open Access |
| contents | Addition of sodium malonate alters the morphology and increases the critical flux during tangential flow filtration of precipitated immunoglobulins Ali Behboudi Mirko Minervini Zachary S. Badinger William W. Haddad Andrew L. Zydney Protein Science AbstractRecent studies have demonstrated that one can control the packing density, and in turn the filterability, of protein precipitates by changing the pH and buffer composition of the precipitating solution to increase the structure/order within the precipitate. The objective of this study was to examine the effect of sodium malonate, which is known to enhance protein crystallizability, on the morphology of immunoglobulin precipitates formed using a combination of ZnCl2 and polyethylene glycol. The addition of sodium malonate significantly stabilized the precipitate particles as shown by an increase in melting temperature, as determined by differential scanning calorimetry, and an increase in the enthalpy of interaction, as determined by isothermal titration calorimetry. The sodium malonate also increased the selectivity of the precipitation, significantly reducing the coprecipitation of DNA from a clarified cell culture fluid. The resulting precipitate had a greater packing density and improved filterability, enabling continuous tangential flow filtration with minimal membrane fouling relative to precipitates formed under otherwise identical conditions but in the absence of sodium malonate. These results provide important insights into strategies for controlling precipitate morphology to enhance the performance of precipitation‐filtration processes for the purification of therapeutic proteins. 10.1002/pro.5010 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| doi_str_mv | 10.1002/pro.5010 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_pro_5010 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Addition of sodium malonate alters the morphology and increases the critical flux during tangential flow filtration of precipitated immunoglobulins Ali Behboudi Mirko Minervini Zachary S. Badinger William W. Haddad Andrew L. Zydney Protein Science Addition of sodium malonate alters the morphology and increases the critical flux during tangential flow filtration of precipitated immunoglobulins Ali Behboudi Mirko Minervini Zachary S. Badinger William W. Haddad Andrew L. Zydney Protein Science AbstractRecent studies have demonstrated that one can control the packing density, and in turn the filterability, of protein precipitates by changing the pH and buffer composition of the precipitating solution to increase the structure/order within the precipitate. The objective of this study was to examine the effect of sodium malonate, which is known to enhance protein crystallizability, on the morphology of immunoglobulin precipitates formed using a combination of ZnCl2 and polyethylene glycol. The addition of sodium malonate significantly stabilized the precipitate particles as shown by an increase in melting temperature, as determined by differential scanning calorimetry, and an increase in the enthalpy of interaction, as determined by isothermal titration calorimetry. The sodium malonate also increased the selectivity of the precipitation, significantly reducing the coprecipitation of DNA from a clarified cell culture fluid. The resulting precipitate had a greater packing density and improved filterability, enabling continuous tangential flow filtration with minimal membrane fouling relative to precipitates formed under otherwise identical conditions but in the absence of sodium malonate. These results provide important insights into strategies for controlling precipitate morphology to enhance the performance of precipitation‐filtration processes for the purification of therapeutic proteins. 10.1002/pro.5010 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| title | Addition of sodium malonate alters the morphology and increases the critical flux during tangential flow filtration of precipitated immunoglobulins |
| topic | Protein Science |
| url | https://onlinelibrary.wiley.com/doi/10.1002/pro.5010 |