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Published on: September 7, 2019
Cell surface clicking of antibody-recruiting polymers to metabolically azide-labeled cancer cells
Annemiek Uvyn1, Ruben De Coen, Olivier De Wever
1Department of Pharmaceutics, Ghent University, Ghent, Belgium. br.degeest@ugent.be.
Abstract:
Triggering antibody-mediated innate immune mechanisms to kill cancer cells is an attractive therapeutic avenue. In this context, recruitment of endogenous antibodies to the cancer cell surface could be a viable alternative to the use of monoclonal antibodies. We report on antibody-recruiting polymers containing multiple antibody-binding hapten motifs and cyclooctynes that can covalently conjugate to azides introduced onto the glycocalyx of cancer cells by metabolic labeling with azido sugars.
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Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
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