Site-Selective Antibody Conjugation with Dibromopyrazines.
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.
Szepesi Kovács Dénes, Pásztor Bettina, Ábrányi-Balogh Péter, Petri László, Imre Tímea, Simon József, Tátrai Enikő, Várady György, Tóvári József, Szijj Peter A, Keserű György M
2024
BIOCONJUGATE CHEMISTRY 1043-1802 1520-4812