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  • CBTF: new amine-to-thiol coupling reagent for preparation of antibody conjugates with increased plasma stability.

CBTF: new amine-to-thiol coupling reagent for preparation of antibody conjugates with increased plasma stability.

Bioconjugate chemistry (2015-01-24)
Sergii Kolodych, Oleksandr Koniev, Zoljargal Baatarkhuu, Jean-Yves Bonnefoy, François Debaene, Sarah Cianférani, Alain Van Dorsselaer, Alain Wagner
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
CBTF
Sigma-Aldrich
APN-Maleimide
Sigma-Aldrich
APN-COCI
Sigma-Aldrich
APN-Azide, 95%