A scaling relationship between thermodynamic and hydrodynamic interactions in protein solutions.
| Autor: | Kingsbury JS; Global CMC Development, Sanofi, Framingham, Massachusetts. Electronic address: jonathan.kingsbury@sanofi.com., Starr CG; Global CMC Development, Sanofi, Framingham, Massachusetts., Gokarn YR; Global CMC Development, Sanofi, Framingham, Massachusetts. |
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| Jazyk: | angličtina |
| Zdroj: | Biophysical journal [Biophys J] 2024 Nov 19; Vol. 123 (22), pp. 3871-3883. Date of Electronic Publication: 2024 Oct 02. |
| DOI: | 10.1016/j.bpj.2024.09.032 |
| Abstrakt: | Weak protein interactions are associated with a broad array of biological functions and are often implicated in molecular dysfunction accompanying human disease. In addition, these interactions are a critical determinant in the effective manufacturing, stability, and administration of biotherapeutic proteins. Despite their prominence, much remains unknown about how molecular attributes influence the hydrodynamic and thermodynamic contributions to the overall interaction mechanism. To systematically probe these contributions, we have evaluated self-interaction in a diverse set of proteins that demonstrate a broad range of behaviors from attractive to repulsive. Analysis of the composite trending in the data provides a convenient interconversion among interaction parameters measured from the concentration dependence of the molecular weight, diffusion coefficient, and sedimentation coefficient, as well as insight into the relationship between thermodynamic and hydrodynamic interactions. We find relatively good agreement between our data and a model for interacting hard spheres in the range of weak self-association. In addition, we propose an empirically derived, general scaling relationship applicable across a broad range of self-association and repulsive behaviors. Competing Interests: Declaration of interests The authors were employees of Sanofi during the work described in this manuscript and may hold shares and/or stock options in the company. In response to reasonable requests, noncommercially available materials and experimental protocols, that Sanofi has the right to provide, will be made available to not-for-profit or academic requesters upon completion of a material transfer agreement. Requests may be made by contacting the corresponding author. (Copyright © 2024 Biophysical Society. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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