Deamidation Can Compromise Antibody Colloidal Stability and Enhance Aggregation in a pH-Dependent Manner
| Autor: | Tapan K. Das, Gregory V. Barnett, Charles G. Starr, Thomas R. Slaney, Peter M. Tessier, Magfur E. Alam |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
medicine.drug_class
Drug Compounding Pharmaceutical Science Ph dependent Metal Nanoparticles 02 engineering and technology Monoclonal antibody 030226 pharmacology & pharmacy 03 medical and health sciences Colloid Protein Aggregates 0302 clinical medicine Drug Stability Drug Discovery medicine Humans Transition Temperature Deamidation Chromatography biology Chemistry Chemical modification Antibodies Monoclonal Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology Dynamic Light Scattering Solubility Drug Design Immunoglobulin G Biophysics biology.protein Molecular Medicine Physical stability Chemical stability Gold Antibody Asparagine 0210 nano-technology Hydrophobic and Hydrophilic Interactions |
| Zdroj: | Molecular pharmaceutics. 16(5) |
| ISSN: | 1543-8392 |
| Popis: | Monoclonal antibodies must be both chemically and physically stable to be developed into safe and effective drugs. Although there has been considerable progress in separately understanding the molecular determinants of antibody chemical and physical stability, it remains poorly understood how defects in one property (e.g., chemical stability) impact the other property (e.g., physical stability). Here, we have investigated the impact of a common chemical modification (deamidation) on the physical stability of two monoclonal antibodies as a function of pH (from pH 3.8 to 7.4). Interestingly, we find that deamidation has significant, antibody-specific impacts on physical stability at low pH values that are common during antibody purification. Deamidation causes increases in self-association and/or aggregation at low pH (3.8), and a key contributor to this behavior appears to be deamidation-dependent increases in antibody hydrophobicity at low pH. Our findings highlight pH-dependent impacts of deamidation on antibody colloidal stability and aggregation, which are important to understand in order to improve the development and production of potent antibody therapeutics with high chemical and physical stabilities. |
| Databáze: | OpenAIRE |
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