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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.

Authors

Cristina M. A. Alonso

Alessandro Palumbo

Aaron J. Bullous

Francesca Pretto

Dario Neri

Professor Ross Boyle R.W.Boyle@hull.ac.uk
Professor of Biological Chemistry/ Module Coordinator for Biological Macromolecules/ Biological Safety and Genetic Modifications Committee Member

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.

Journal Article Type Article
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
Institution 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
DOI https://doi.org/10.1021/bc9003537
Keywords Biotechnology; Organic Chemistry; Bioengineering; Pharmacology; Pharmaceutical Science; Biomedical Engineering
Publisher URL https://pubs.acs.org/doi/abs/10.1021/bc9003537