Fiche publication
Date publication
février 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CIANFERANI Sarah
,
Dr VAN DORSSELAER Alain
,
Dr WAGNER Alain
Tous les auteurs :
Kolodych S, Koniev O, Baatarkhuu Z, Bonnefoy JY, Debaene F, Cianferani S, Van Dorsselaer A, Wagner A
Lien Pubmed
Résumé
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.
Référence
Bioconjug Chem. 2015 Feb 18;26(2):197-200
