Journal
CHEMICAL COMMUNICATIONS
Volume 47, Issue 38, Pages 10752-10754Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c1cc14164c
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A novel pathway for ex vivo maytansinoid release from thioether linked antibody maytansinoid conjugates (AMCs) upon incubation in human plasma has been identified. A thioether succinimide-linked AMC can undergo chemical oxidation followed by sulfoxide elimination under mild aqueous conditions (pH 5.5-7.5, 37 degrees C). Oxidized thioether-linked AMCs exhibit high, target-specific cytotoxicity toward cancer cells.
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