کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1216008 | 1494189 | 2006 | 9 صفحه PDF | دانلود رایگان |
The susceptible degradation sites of therapeutic proteins are routinely assessed under accelerated conditions such as exposure to chemicals or incubation at elevated temperature or a combination of both. A fully human monoclonal IgG1 antibody was characterized after incubation at 40 °C for 6 months by employing mass spectrometry and chromatography analyses. It was found that deamidation, fragmentation and N-terminal glutamate cyclization to form pyroglutamate are the major degradation pathways. Three major deamidation sites were identified and one site in a small tryptic peptide accounted for more than 80% of the total. Peptide cleavage was observed at several positions between different pairs of amino acids. Most of the cleavage sites were located in the hinge or other flexible regions of the IgG molecule.
Journal: Journal of Chromatography B - Volume 837, Issues 1–2, 6 June 2006, Pages 35–43