National Laboratories Excellence program (under the National Tumor Biology Laboratory
Project(NLP-17)
(NKFIH PD124598)
(PD143427)
(ÚNKP-23-4)
In recent years, antibody conjugates have evolved as state-of-the-art options for
diagnostic and therapeutic applications. During site-selective antibody conjugation,
incomplete rebridging of antibody chains limits the homogeneity of conjugates and
calls for the development of new rebridging agents. Herein, we report a dibromopyrazine
derivative optimized to reach highly homogeneous conjugates rapidly and with high
conversion on rebridging of trastuzumab, even providing a feasible route for antibody
modification in acidic conditions. Furthermore, coupling a fluorescent dye and a cytotoxic
drug resulted in effective antibody conjugates with excellent serum stability and
in vitro selectivity, demonstrating the utility of the dibromopyrazine rebridging
agent to produce on-demand future antibody conjugates for diagnostic or therapeutic
applications.
