A novel pathway for maytansinoid release from thioether linked antibody-drug conjugates (ADCs) under oxidative conditions
A novel pathway for maytansinoid release from thioether linked antibody-drug conjugates (ADCs) under oxidative conditions
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DOI：
10.1039/c1cc14164c
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发表时间：
2011-01-01
影响因子：
4.9
通讯作者：
Singh, Rajeeva
中科院分区：
文献类型：
--
作者：
Fishkin, Nathan;Maloney, Erin K.;Singh, Rajeeva
已经鉴定了在人血浆中孵育后从硫醚连接的抗体美登木素生物碱缀合物（AMC）中离体释放美登木素生物碱的新途径。硫醚琥珀酰亚胺连接的AMC可以在温和的水性条件（pH 5.5-7.5，37 ° C）下进行化学氧化，然后进行亚砜消除。氧化硫醚连接的AMC对癌细胞表现出高的靶向特异性细胞毒性。
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.