Figure 1.

(A) Structures of ADCs bearing disulfide linkers and the metabolites that are formed from their proteolysis in catabolic vesicles followed by disulfide cleavage and S-methylation. DM indicates the depicted maytansinoid moiety, derivatizable on the N-methyl alanyl amine. (B) Structures of ADCs with peptide-anilino linkers and the metabolite that is formed from proteolysis. (C) Structures of the new ADCs bearing peptide-immolative linkers and the metabolites that are expected to be formed in catabolic vesicles followed by S-methylation. Bracketed letters (l or d) indicate alanyl stereochemistry in the direction from antibody toward the maytansinoid. (D) Structures formed if the sulfur atoms of 12a–12c are oxidized.