Self-hydrolyzing maleimides improve the stability and pharmacological properties of antibody-drug conjugates

@article{Lyon2014SelfhydrolyzingMI,
  title={Self-hydrolyzing maleimides improve the stability and pharmacological properties of antibody-drug conjugates},
  author={Robert P. Lyon and Jocelyn R. Setter and Tim D. Bovee and Svetlana O. Doronina and Joshua H. Hunter and Martha E. Anderson and Cindy Balasubramanian and Steve Duniho and Chris I Leiske and Fu Li and Peter D. Senter},
  journal={Nature Biotechnology},
  year={2014},
  volume={32},
  pages={1059-1062}
}
Many antibody-drug conjugates (ADCs) are unstable in vivo because they are formed from maleimide-containing components conjugated to reactive thiols. These thiosuccinimide linkages undergo two competing reactions in plasma: elimination of the maleimide through a retro-Michael reaction, which results in loss of drug-linker from the ADC, and hydrolysis of the thiosuccinimide ring, which results in a derivative that is resistant to the elimination reaction. In an effort to create linker… 
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