In-Depth Characterization of a Pro-Antibody–Drug Conjugate by LC–MS
作者： Boning Liu , Huaizu Guo , Junjie Zhang , Jingya Xue , Yun Yang
DOI: 10.1021/ACS.MOLPHARMACEUT.6B00280
关键词:
摘要: Pro-antibody–drug conjugate (PDC) is a hybrid structural format of immunoconjugate, where the complexity pro-antibody and intrinsic heterogeneity ADCs impose prominent analytical challenge to in-depth characterization PDCs. In present study, we successfully prepared characterized PanP–DM1 as model PDCs, which an anti-EGFR following conjugation with DM1 at lysine residues. The drug-to-antibody ratio (DAR) was determined by LC–MS after deglycosylation, verified UV/vis spectroscopy. Following reduction or IdeS digestion, fragments linked were investigated middle-down mass spectrometry. Furthermore, more than 20 modified sites peptide mapping trypsin digestion. Additionally, ten glycoforms also identified quantified. summary, critical quality attributes (CQAs) PDCs including DAR, drug load distribution, wer...
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