Relative abundance of disulfide cleavage
and immolation products
over time. Products were monitored by LC/MS from incubations of linker
drugs 1, 2, and 7 in the presence
of cysteine (0.2 mM, A1, A2, A7; and 0.03 mM, B1, B2, B7) or glutathione
(4 mM, C1, C2, C7; and 0.03 mM, D1, D2, D7) at pH 7.0 and 37 °C. P = starting linker drugs 1 (methyl-), 2 (cyclopropyl-), and 7 (cyclobutyl-). Payload
= PBD dimer 4. Thiol-GSH or -cysteine = 1a or 1b (methyl-), 2a or 2b (cyclopropyl-), or 7a or 7b (cyclobutyl).
Thiol = 1d, 2d, or 7d.