Site-specific and stoichiometric conjugation of cationic porphyrins to antiangiogenic monoclonal antibodies

Alonso, Cristina M. A.; Palumbo, Alessandro; Bullous, Aaron J.; Pretto, Francesca; Neri, Dario; Boyle, Ross W.

Abstract

Synthesis of three new cationic thiol-reactive maleimide-porphyrin derivatives and their use in site-specific conjugation to monoclonal antibodies is reported. The selective reactivity toward thiols is demonstrated using competition experiments, where both thiols and amines are present. This selectivity was used to successfully achieve specific conjugation of two porphyrins to cysteine residues present in the antiangiogenic antibody L19, expressed in small immunoprotein (SIP) format. The effect of length and hydrophilicity of the linkage between porphyrin and maleimide was also investigated, and maximum photocytotoxicity was achieved with the longest and most hydrophilic chain. Immunoreactivity and in vitro photocytotoxicity for these well-characterized porphyrin-antibody conjugates are described.

Citation

Alonso, C. M. A., Palumbo, A., Bullous, A. J., Pretto, F., Neri, D., & Boyle, R. W. (2010). Site-specific and stoichiometric conjugation of cationic porphyrins to antiangiogenic monoclonal antibodies. Bioconjugate chemistry, 21(2), 302-313. https://doi.org/10.1021/bc9003537

• Journal Article Type: Article
• Online Publication Date: Jan 14, 2010
• Publication Date: Feb 17, 2010
• Journal: BIOCONJUGATE CHEMISTRY
• Print ISSN: 1043-1802
• Electronic ISSN: 1520-4812
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 21
• Issue: 2
• Pages: 302-313
• DOI: https://doi.org/10.1021/bc9003537
• Keywords: Biotechnology; Organic Chemistry; Bioengineering; Pharmacology; Pharmaceutical Science; Biomedical Engineering
• Public URL: https://hull-repository.worktribe.com/output/387112
• Publisher URL: https://pubs.acs.org/doi/abs/10.1021/bc9003537