Light-Induced Histidine Adducts to an IgG1 Molecule Via Oxidized Histidine Residue and the Potential Impact of Polysorbate-20 Concentration
| Autor: | Cynthia P. Quan, Christian Schöneich, John Wang, Yung-Hsiang Kao, Ming Lei |
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| Rok vydání: | 2021 |
| Předmět: |
Tris
Protein Denaturation Protein Conformation Drug Compounding Polysorbates Pharmaceutical Science Excipient 02 engineering and technology 030226 pharmacology & pharmacy Adduct Excipients Protein Aggregates 03 medical and health sciences chemistry.chemical_compound Residue (chemistry) Oxidants Photochemical 0302 clinical medicine Nucleophile Tandem Mass Spectrometry medicine Histidine Pharmacology (medical) Amino Acid Sequence Chromatography High Pressure Liquid Pharmacology Singlet oxygen Organic Chemistry 021001 nanoscience & nanotechnology Combinatorial chemistry chemistry Immunoglobulin G Molecular Medicine Polysorbate 20 0210 nano-technology Oxidation-Reduction Biotechnology medicine.drug |
| Zdroj: | Pharmaceutical Research. 38:491-501 |
| ISSN: | 1573-904X 0724-8741 |
| DOI: | 10.1007/s11095-021-03010-2 |
| Popis: | Histidine (His) undergoes light-induced reactions such as oxidation, crosslinking and addition. These reactions are initiated by singlet oxygen (1O2) to generate His photo-oxidation products, which are subject to nucleophilic attack by a non-oxidized His residue from another protein or by nucleophilic buffer components such as Tris and His. This report aims to identify light-induced His-adducts to a monoclonal antibody (mAb-1) due to the reaction of His molecules in the buffer with the photooxidized His residues under ICH light conditions. Since polysorbate-20 (PS-20) is a commonly used excipient in biotherapeutics formulation, it is also important to study the impact of PS-20 concentration on protein photostability. We identified and characterized light-induced His-adducts of mAb-1 by LC-MS/MS. We showed that the levels of light-induced His-adducts generally correlate with the solvent accessibility of His residues in the protein. In addition, the presence of PS-20 at concentrations commonly used in protein drug formulations can significantly increase the levels of light-induced His-adducts. Since His residues are present in a conserved region in the Fc domain, and may be present in the complementarity-determining region (CDR), the impact on the biological functions of the His-adducts observed here should be further studied to evaluate the risk of their presence. |
| Databáze: | OpenAIRE |
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