Kolodych Sergii, Koniev Oleksandr, Baatarkhuu Zoljargal, Bonnefoy Jean-Yves, Debaene François, Cianférani Sarah, Van Dorsselaer Alain, Wagner Alain
Laboratory of Functional ChemoSystems (UMR 7199), Labex Medalis, University of Strasbourg , 67081 Strasbourg, France.
Bioconjug Chem. 2015 Feb 18;26(2):197-200. doi: 10.1021/bc500610g. Epub 2015 Jan 23.
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.
胺与硫醇的偶联是制备抗体药物偶联物（ADC）最常用的途径。通常通过使用一端具有活性酯而另一端具有马来酰亚胺基团的异双功能试剂来实现。然而，最近发现基于马来酰亚胺的偶联物在血液循环中的稳定性有限，这可能会损害偶联物的治疗效果。为了解决这个问题，我们开发了一种用于胺与硫醇偶联的异双功能试剂4-((4-(氰基乙炔基)苯甲酰基)氧基)-2,3,5,6-四氟苯磺酸钠（CBTF）。它包含一个最近描述的3-芳基丙腈（APN）官能团来取代马来酰亚胺，并能够制备出稳定性显著的偶联物。使用该试剂制备了一系列抗体-染料偶联物，与基于马来酰亚胺的偶联物相比，它们在人血浆中表现出更高的稳定性。
