Phenyldivinylsulfonamides for the construction of antibody-drug conjugates with controlled four payloads
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作者
Wei, Ding; Jiang, Yuecheng; Mao, Yurong; Xu, Zili; Chen, Jiakang; Gao, Xiuxia; Li, Jiusheng; Jiang, Biao; Chen, Hongli
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刊物名称
BIOORGANIC CHEMISTRY
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年、卷、文献号
2023, 134, 1090-2120
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关键词
Wei, Ding; Jiang, Yuecheng; Mao, Yurong; Xu, Zili; Chen, Jiakang; Gao, Xiuxia; Li, Jiusheng; Jiang, Biao; Chen, Hongli
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摘要
Phenyldivinylsulfonamides emerged from a series of divinylsulfonamides, demonstrating their ability to effectively re-bridge disulfide bonds. This kind of linkers was attached to monomethyl auristatin E (MMAE) and further conjugated with a model antibody, trastuzumab. After optimization, the linker 20 can deliver stable and highly homogenous DAR (Drug-to-Antibody Ratio) four antibody-drug conjugates (ADCs). The method was also applicable for other IgG1 antibodies to obtain ADCs with controlled four payloads. Moreover, the MMAE-bearing ADC is potent, selective and efficacious against target cell lines.
