Figure 4.

Shielding effect . (a) Chemical structures of the standard linker (SL), long linker (LL), and auristatin E derivatives (AE). SLAE is the combination of SL and AE, in which X is a methyl substituent. LLAE is the combination of LL and AE, in which X is a hydrogen substituent. The dashes at the C-terminus of the linker and at the N-terminus of the drug represent the bond between the linker and the drug. (b) Differences in retention time (RT) between ADCs based on LLAE and ADCs based on SLAE were calculated as follows: RT difference = RT_{LLAE-based ADC}—RT_{SLAE-based ADC}. (c) HIC chromatograms (214 nm) of ADCs based on mAb1 or mAb2, with designs C, A, and B (from top to bottom), containing LLAE (DBCO-C6-PEG8-VC-PABC-AE). The arrows indicate the corresponding DAR species in each sample. For the chromatograms presented here, 125 ng of mAb1 wt or mAb2 wt were added to the sample (5 μg) as internal standard before injection.