title: CBTF: new amine-to-thiol coupling reagent for preparation of antibody conjugates with increased plasma stability.
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.
authors.affiliation: Laboratory of Functional ChemoSystems (UMR 7199), Labex Medalis, University of Strasbourg , 67081 Strasbourg, France.
authors.forename: Sergii
authors.initials: S
authors.lastname: Kolodych
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Koniev
authors.forename: Zoljargal
authors.initials: Z
authors.lastname: Baatarkhuu
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Bonnefoy
authors.forename: François
authors.initials: F
authors.lastname: Debaene
authors.forename: Sarah
authors.initials: S
authors.lastname: Cianférani
authors.forename: Alain
authors.initials: A
authors.lastname: Van Dorsselaer
authors.forename: Alain
authors.initials: A
authors.lastname: Wagner
mesh_terms: D000588:Amines / Q000737:chemistry*; D001555:Benzene Derivatives / Q000737:chemistry*; D002460:Cell Line; D003432:Cross-Linking Reagents / Q000737:chemistry*; D054879:Halogenation; D006801:Humans; D018796:Immunoconjugates / Q000097:blood / Q000737:chemistry*; D008301:Maleimides / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D000588:Amines; D001555:Benzene Derivatives; D003432:Cross-Linking Reagents; D018796:Immunoconjugates; D008301:Maleimides; D013438:Sulfhydryl Compounds; C043592:maleimide