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 <i>in vitro</i> selectivity, demonstrating the utility of the dibromopyrazine rebridging agent to produce on-demand future antibody conjugates for diagnostic or therapeutic applications.
Authors
- György Várady (ORCID: https://orcid.org/0000-0003-2012-9680)
- Péter Ábrányi‐Balogh (ORCID: https://orcid.org/0000-0002-9284-5160)
- György M. Keserű (ORCID: https://orcid.org/0000-0003-1039-7809)
- Tı́mea Imre (ORCID: https://orcid.org/0000-0001-5830-8137)
- Péter A. Szijj (ORCID: https://orcid.org/0000-0002-2944-2676)
- László Petri (ORCID: https://orcid.org/0000-0001-9881-5096)
- Dénes Szepesi Kovács
- József Tóvári (ORCID: https://orcid.org/0000-0002-5543-3204)
- Bettina Pásztor
- Enikő Tátrai
- József Simon
Institutions
- Eötvös Loránd University (HU)
- Budapest University of Technology and Economics (HU)
- National Institute of Oncology (HU)
- University College London (GB)
- HUN-REN Research Centre for Natural Sciences (HU)
Publication Details
- Journal
- Bioconjugate Chemistry
- Published
- 2024-08-16
- DOI
- https://doi.org/10.1021/acs.bioconjchem.4c00296
- Citations
- 5
- Primary Topic
- Monoclonal and Polyclonal Antibodies Research
- Type
- article
- Field-Weighted Citation Impact
- 2.02
Funders
- Budapesti Műszaki és Gazdaságtudományi Egyetem
- University College London
- Magyar Tudományos Akadémia
- Eötvös Loránd Tudományegyetem
- Nemzeti Kutatási Fejlesztési és Innovációs Hivatal
- Nemzeti Kutatási, Fejlesztési és Innovaciós Alap