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Wiley, Angewandte Chemie International Edition, 28(53), p. 7179-7182, 2014

DOI: 10.1002/anie.201402606

Wiley, Angewandte Chemie, 28(126), p. 7307-7310, 2014

DOI: 10.1002/ange.201402606

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Preparation of Well-Defined Antibody–Drug Conjugates through Glycan Remodeling and Strain-Promoted Azide–Alkyne Cycloadditions

Journal article published in 2014 by Xiuru Li, Tao Fang, Geert‐Jan Boons ORCID
This paper is available in a repository.
This paper is available in a repository.

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Abstract

Antibody–drug conjugates hold considerable promise as anticancer agents, however, producing them remains a challenge and there is a need for mild, broadly applicable, site-specific conjugation methods that yield homogenous products. It was envisaged that enzymatic remodeling of the oligosaccharides of an antibody would enable the introduction of reactive groups that can be exploited for the site-specific attachment of cytotoxic drugs. This is based on the observation that glycosyltransferases often tolerate chemical modifications in their sugar nucleotide substrates, thus allowing the installation of reactive functionalities. An azide was incorporated because this functional group is virtually absent in biological systems and can be reacted by strain-promoted alkyne–azide cycloaddition. This method, which does not require genetic engineering, was used to produce an anti-CD22 antibody modified with doxorubicin to selectively target and kill lymphoma cells.