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Bioorthogonal Decaging Reactions for Targeted Drug Activation

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Bioorthogonal decaging reactions are highly selective transformations which involve the cleavage of a protecting group from a molecule of interest. Decaging reactions can be classified into subgroups depending on the nature of the trigger; they can be photo-, metal- or small molecule-triggered. Due to their highly selective and biocompatible nature, they can be carried out in living systems as they do not interfere with any endogenous processes. This gain-of-function allows controlled activation of proteins and release of fluorophores and drugs in vivo. Although there are many examples of fluorophore/protein release, this review focuses on the application of bioorthogonal decaging reactions for targeted drug activation. One strategy for targeted drug delivery is tissue-selective activation of prodrugs and antibody–drug conjugates (ADCs). Bioorthogonal decaging provides a highly selective, controllable method for activating prodrugs and ADCs, reducing toxicity due to the off-target drug release that occurs in endogenous activation strategies. Here we focus on the development of bifunctional linkers that enable studies of bioorthogonal chemistry for activation of ADCs.
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Keywords: ANTIBODY–DRUG CONJUGATES; BIFUNCTIONAL LINKERS; BIOORTHOGONAL DECAGING; TARGETED DRUG DELIVERY

Document Type: Research Article

Affiliations: 1: Department of Chemistry, University of Cambridge Lensfield Road, CB2 1EW Cambridge, UK 2: Department of Chemistry, University of Cambridge Lensfield Road, CB2 1EW Cambridge, UK, Instituto de Medicina Molecular Faculdade de Medicina, Universidade de Lisboa Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal; ;[email protected], Email: [email protected]

Publication date: 01 November 2018

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  • International Journal for Chemistry and Official Membership Journal of the Swiss Chemical Society (SCS) and its Divisions

    CHIMIA, a scientific journal for chemistry in the broadest sense, is published 10 times a year and covers the interests of a wide and diverse readership. Contributions from all fields of chemistry and related areas are considered for publication in the form of Review Articles and Notes. A characteristic feature of CHIMIA are the thematic issues, each devoted to an area of great current significance.

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