CBTF: new amine-to-thiol coupling reagent for preparation of antibody conjugates with increased plasma stability.
Sergii Kolodych, Oleksandr Koniev, Zoljargal Baatarkhuu, Jean-Yves Bonnefoy, François Debaene, Sarah Cianférani, Alain Van Dorsselaer, Alain Wagner
文献索引：Bioconjug. Chem. 26(2) , 197-200, (2015)
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摘要
Amine-to-thiol coupling is the most common route for the preparation of antibody-drug conjugates (ADC). It is usually achieved by using heterobifunctional reagents possessing an activated ester at one end and a maleimide group at the other. However, maleimide-based conjugates were recently revealed to have limited stability in blood circulation, which can compromise therapeutic efficacy of the conjugate. To address this issue, we have developed a heterobifunctional reagent, sodium 4-((4-(cyanoethynyl)benzoyl)oxy)-2,3,5,6-tetrafluorobenzenesulfonate (CBTF), for amine-to-thiol coupling. It comprises a recently described 3-arylpropionitrile (APN) function in replacement of maleimide and allows for the preparation of remarkably stable conjugates. A series of antibody-dye conjugates have been prepared using this reagent and shown superior stability in human blood plasma compared to maleimide-derived conjugates.