Figure 2
From: Statistical characterization of therapeutic protein modifications
Representative extracted ion chromatograms for peptides from (a) AI and (b) ADC reference samples, and (c) AI and (d) ADC forced degradation (e.g., 3 mM AAPH) samples. Most peptides, including the unmodified peptide VDNALQSGNSQESVTEQDSK that can be used for normalization, were unaffected by the conjugation of linker drug. On the other hand, the linker-drug-modified peptides such as SFNRGEC were only observed in the ADC. In the ADC, the cysteine in this peptide was observed with carboxymethylation (+58 Da), vcMMAE- (+1315 Da), and vcMMAEhydro (+1333 Da) modifications. In the AI, the cysteine was fully carboxymethylated and no linker-drug modifications were observed. Comparisons of non-linker-drug modifications between reference samples provided negative control for differential site occupancy analysis while comparisons between reference samples versus their forced degradation samples provided positive controls.
