Kroon D J, Baldwin-Ferro A, Lalan P
R. W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey 08869.
Pharm Res. 1992 Nov;9(11):1386-93. doi: 10.1023/a:1015894409623.
A peptide mapping procedure was developed to locate regions of a monoclonal antibody, OKT3, that undergo chemical modification as the molecule degrades upon storage. The structures of these peptide degradation products were investigated. Deamidation at specific asparagine residues and oxidation of a cysteine and several methionines were found to be major routes of OKT3 degradation. A unique chain cross-linked degradation product was also observed and characterized. Changing the storage conditions of the antibody affected the relative distribution of degradation products. These results were useful in the development of more stable formulations for OKT3, and the methods can be used in the characterization of other monoclonal antibodies intended for therapeutic use.
开发了一种肽图谱分析方法，以定位单克隆抗体OKT3中在储存过程中分子降解时发生化学修饰的区域。对这些肽降解产物的结构进行了研究。发现特定天冬酰胺残基的脱酰胺作用以及一个半胱氨酸和几个甲硫氨酸的氧化是OKT3降解的主要途径。还观察并表征了一种独特的链交联降解产物。改变抗体的储存条件会影响降解产物的相对分布。这些结果有助于开发更稳定的OKT3制剂，并且该方法可用于表征其他用于治疗的单克隆抗体。
