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Regioselective and stoichiometrically controlled conjugation of photodynamic sensitizers to a HER2 targeting antibody fragment

Bryden, Francesca; Maruani, Antoine; Savoie, Huguette; Chudasama, Vijay; Smith, Mark E. B.; Caddick, Stephen; Boyle, Ross W.

Authors

Francesca Bryden

Antoine Maruani

Huguette Savoie

Vijay Chudasama

Mark E. B. Smith

Stephen Caddick



Abstract

The rapidly increasing interest in the synthesis of antibody–drug conjugates as powerful targeted anticancer agents demonstrates the growing appreciation of the power of antibodies and antibody fragments as highly selective targeting moieties. This targeting ability is of particular interest in the area of photodynamic therapy, as the applicability of current clinical photosensitizers is limited by their relatively poor accumulation in target tissue in comparison to healthy tissue. Although synthesis of porphyrin–antibody conjugates has been previously demonstrated, existing work in this area has been hindered by the limitations of conventional antibody conjugation methods. This work describes the attachment of azide-functionalized, water-soluble porphyrins to a tratuzumab Fab fragment via a novel conjugation methodology. This method allows for the synthesis of a homogeneous product without the loss of structural stability associated with conventional methods of disulfide modification. Biological evaluation of the synthesized conjugates demonstrates excellent selectivity for a HER2 positive cell line over the control, with no dark toxicity observed in either case.

Publication Date 2014-02
Journal Bioconjugate chemistry
Print ISSN 1043-1802
Electronic ISSN 1520-4812
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Volume 25
Issue 3
Pages 611-617
Institution Citation Bryden, F., Maruani, A., Savoie, H., Chudasama, V., Smith, M. E. B., Caddick, S., & Boyle, R. W. (2014). Regioselective and stoichiometrically controlled conjugation of photodynamic sensitizers to a HER2 targeting antibody fragment. Bioconjugate chemistry, 25(3), 611-617. https://doi.org/10.1021/bc5000324
DOI https://doi.org/10.1021/bc5000324
Keywords Photodynamic sensitisers; Photodynamic therapy; HER2
Publisher URL http://pubs.acs.org/doi/abs/10.1021/bc5000324
Copyright Statement ©2015 University of Hull
Additional Information This document is the Accepted Manuscript version of a Published Work that appeared in final form in Bioconjugate chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/bc5000324

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