CBTF: New Amine-to-Thiol Coupling Reagent for Preparation of Antibody Conjugates with Increased Plasma Stability

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• 作者：Sergii Kolodych ; Oleksandr Koniev ; Zoljargal Baatarkhuu ; Jean-Yves Bonnefoy ; Fran莽ois Debaene ; Sarah Cianf茅rani ; Alain Van Dorsselaer ; Alain Wagner
• 刊名：Bioconjugate Chemistry
• 出版年：2015
• 出版时间：February 18, 2015
• 年：2015
• 卷：26
• 期：2
• 页码：197-200
• 全文大小：247K
• ISSN：1520-4812

文摘

Amine-to-thiol coupling is the most common route for the preparation of antibody鈥揹rug 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鈥揹ye conjugates have been prepared using this reagent and shown superior stability in human blood plasma compared to maleimide-derived conjugates.