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(A) Sequences of the pHLIP peptides used in this study. The amino acid substitution for the variant pHLIP(D25E) is shown in bold, and the cysteine available for disulfide drug conjugation is shown underlined. (B) Structure of MMAE with a succinimide nitrophenyl-based linker, conjugation to pHLIP via disulfide exchange and the structure of MMAE as released intracellularly after pHLIP insertion and reduction of the disulfide bond.
