Table 2.
Conjugation of various BCN-linker-drugs to azidosugar-remodeled trastuzumab leading to DAR2 ADCs (14–18) or DAR4 ADCs (19 and 5). PG = propylene glycol. For structure of BCN-linker-payload 5, see Figure 4, for structure of 19, see Figure 6, for other structures see ESI
| Entry | Cmpd | R | x | y | Payload | Equiv. | co-solvent | Yield | DAR |
|---|---|---|---|---|---|---|---|---|---|
| 1 | 14 | Cit | 0 | 1 | calicheamicin | 8 | 50% PG | 78% | 1.81 |
| 2 | 15 | Cit | 0 | 1 | Gly-calicheamicin | 6 | 50% PG | 66% | 1.86 |
| 3 | 16 | Ala | 0 | 1 | PBD dimer | 5 | 15% DMF | 79% | 1.79 |
| 4 | 17 | Cit | 1 | 1 | PNU-159,682 | 7 | 25% DMF | 83% | 1.81 |
| 5 | 18 | Cit | 1 | 1 | duocarmycin | 10 | 25% DMF | 79% | 1.82 |
| 6 | 19 | Cit | 0 | 2 | Ahx-maytansine | 8 | 25% DMF | 96% | 3.70 |
| 7 | 5 | Cit | 0 | 2 | MMAE | 7 | 25% DMF | 81% | 3.60 |
A table showing how an antibody can be converted into DAR2 or DAR4 ADC using GlycoConnect™ technology and conjugation of linker-drugs with payloads calicheamicin, PBD dimer, PNU-159,682, duocarmycin, Ahx-maytansine, or MMAE.