Back to Search
Start Over
Specific-Ion Effects on the Aggregation Mechanisms and Protein–Protein Interactions for Anti-streptavidin Immunoglobulin Gamma-1
- Source :
- The Journal of Physical Chemistry B. 119:5793-5804
- Publication Year :
- 2015
- Publisher :
- American Chemical Society (ACS), 2015.
-
Abstract
- Non-native protein aggregation is common in the biopharmaceutical industry and potentially jeopardizes product shelf life, therapeutic efficacy, and patient safety. The present article focuses on the relationship(s) among protein-protein interactions, aggregate growth mechanisms, aggregate morphologies, and specific-ion effects for an anti-streptavidin (AS) immunoglobulin gamma 1 (IgG1). Aggregation mechanisms of AS-IgG1 were determined as a function of pH and NaCl concentration with sodium acetate buffer and compared to previous work with sodium citrate. Aggregate size and shape were determined using a combination of laser light scattering and small-angle neutron or X-ray scattering. Protein-protein interactions were quantified in terms of the protein-protein Kirkwood-Buff integral (G22) determined from static light scattering and in terms of the protein effective charge (Zeff) measured using electrophoretic light scattering. Changing from citrate to acetate resulted in significantly different protein-protein interactions as a function of pH for low NaCl concentrations when the protein displayed positive Zeff. Overall, the results suggest that electrostatic repulsions between proteins were lessened because of preferential accumulation of citrate anions, compared to acetate anions, at the protein surface. The predominant aggregation mechanisms correlated well with G22, indicating that ion-specific effects beyond traditional mean-field descriptions of electrostatic protein-protein interactions are important for predicting qualitative shifts in protein aggregation state diagrams. Interestingly, while solution conditions dictated which mechanisms predominated, aggregate average molecular weight and size displayed a common scaling behavior across both citrate- and acetate-based systems.
- Subjects :
- Streptavidin
Sodium Acetate
Surface Properties
Static Electricity
Sodium Chloride
Protein aggregation
Sodium Citrate
Protein–protein interaction
Protein Aggregates
chemistry.chemical_compound
Static electricity
Sodium citrate
Materials Chemistry
Scattering, Radiation
Static light scattering
Citrates
Colloids
Physical and Theoretical Chemistry
Ions
Hydrogen-Ion Concentration
Surfaces, Coatings and Films
Molecular Weight
Solutions
Crystallography
chemistry
Immunoglobulin G
Hydrodynamics
Biophysics
Electrophoretic light scattering
Sodium acetate
Subjects
Details
- ISSN :
- 15205207 and 15206106
- Volume :
- 119
- Database :
- OpenAIRE
- Journal :
- The Journal of Physical Chemistry B
- Accession number :
- edsair.doi.dedup.....c665188ba178f582649df137ce8b1d2e