Wei Ding, Jiang Yuecheng, Mao Yurong, Xu Zili, Chen Jiakang, Gao Xiuxia, Li Jiusheng, Jiang Biao, Chen Hongli
Green Chemical Engineering Technology Research Center, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China; Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 393 Middle Huaxia Road, Pudong, Shanghai, 201210, China; University of Chinese Academy of Sciences, 19A Yuquan Road, Shijingshan District, Beijing 100049, China.
Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 393 Middle Huaxia Road, Pudong, Shanghai, 201210, China; School of Physical Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Pudong, Shanghai 201210, China.
Bioorg Chem. 2023 May;134:106463. doi: 10.1016/j.bioorg.2023.106463. Epub 2023 Mar 12.
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.
苯基二乙烯基磺酰胺源自一系列二乙烯基磺酰胺，显示出它们有效重新桥连二硫键的能力。这种连接子连接到单甲基澳瑞他汀E（MMAE）上，并进一步与模型抗体曲妥珠单抗偶联。经过优化，连接子20可以提供稳定且高度均一的药物与抗体比（DAR）为4的四种抗体药物偶联物（ADC）。该方法也适用于其他IgG1抗体，以获得具有可控四种载药量的ADC。此外，携带MMAE的ADC对靶细胞系具有强效、选择性和有效性。
