The Use of a 2,2'-Azobis (2-Amidinopropane) Dihydrochloride Stress Model as an Indicator of Oxidation Susceptibility for Monoclonal Antibodies
| Autor: | Amy Hilderbrand, Daniel Bregante, Nisana Andersen, Wayman Chan, Michelle Z. Dion, Y. John Wang, Danielle L. Leiske, Cleo M. Salisbury |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Free Radicals medicine.drug_class Amidines Pharmaceutical Science Peptide Oxidative phosphorylation Monoclonal antibody Protein oxidation 030226 pharmacology & pharmacy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine 2 2'-Azobis(2-amidinopropane) dihydrochloride Alkyl chemistry.chemical_classification Antibodies Monoclonal Proteins Combinatorial chemistry 030104 developmental biology chemistry Biochemistry Reagent Forced degradation Peptides Oxidation-Reduction |
| Zdroj: | Journal of Pharmaceutical Sciences. 107:550-558 |
| ISSN: | 0022-3549 |
| Popis: | Protein oxidation is a major pathway for degradation of biologic drug products. Past literature reports have suggested that 2,2-azobis (2-amidinopropane) dihydrochloride (AAPH), a free radical generator that produces alkoxyl and alkyl peroxyl radicals, is a useful model reagent stress for assessing the oxidative susceptibility of proteins. Here, we expand the applications of the AAPH model by pairing it with a rapid peptide map method to enable site-specific studies of oxidative susceptibility of monoclonal antibodies and their derivatives for comparison between formats, the evaluation of formulation components, and comparisons across the stress models. Comparing the free radical-induced oxidation model by AAPH with a light-induced oxidation model suggests that light-sensitive residues represent a subset of AAPH-sensitive residues and therefore AAPH can be used as a preliminary screen to highlight molecules that need further assessment by light models. In sum, these studies demonstrate that AAPH stress can be used in multiple ways to evaluate labile residues and oxidation sensitivity as it pertains to developability and manufacturability. |
| Databáze: | OpenAIRE |
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