Specific-Ion Effects on the Aggregation Mechanisms and Protein–Protein Interactions for Anti-streptavidin Immunoglobulin Gamma-1

• DOI: 10.1021/acs.jpcb.5b01881
• Publication Date: 2015-04-17T15:58:33Z
• Authors: Gregory V. Barnett; Vladimir I. Razinkov; Bruce A. Kerwin; Thomas M. Laue; Andrea H. Woodka; Paul D. Butler; Tatiana Perevozch...; Christopher J. Ro...
• Keywords: Streptavidin

Non-native protein aggregation is common in the biopharmaceutical industry and potentially jeopardizes product shelf life, therapeutic efficacy, patient safety. The present article focuses on relationship(s) among protein-protein interactions, aggregate growth mechanisms, morphologies, specific-ion effects for an anti-streptavidin (AS) immunoglobulin gamma 1 (IgG1). Aggregation mechanisms of AS-IgG1 were determined as a function pH NaCl concentration with sodium acetate buffer compared to previous work citrate. Aggregate size shape using combination laser light scattering small-angle neutron or X-ray scattering. Protein-protein interactions quantified terms Kirkwood-Buff integral (G22) from static effective charge (Zeff) measured electrophoretic Changing citrate resulted significantly different low concentrations when displayed positive Zeff. Overall, results suggest that electrostatic repulsions between proteins lessened because preferential accumulation anions, at surface. predominant correlated well G22, indicating ion-specific beyond traditional mean-field descriptions are important predicting qualitative shifts state diagrams. Interestingly, while solution conditions dictated which predominated, average molecular weight scaling behavior across both citrate- acetate-based systems.