Bioorthogonal Decaging Reactions for Targeted Drug Activation

Authors

  • Sarah Davies Department of Chemistry, University of Cambridge Lensfield Road, CB2 1EW Cambridge, UK
  • Benjamin J. Stenton Department of Chemistry, University of Cambridge Lensfield Road, CB2 1EW Cambridge, UK
  • Gonçalo J. L. Bernardes 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. gbernardes@medicina.ulisboa.pt gb453@cam.ac.uk

DOI:

https://doi.org/10.2533/chimia.2018.771

Keywords:

Antibody–drug conjugates, Bifunctional linkers, Bioorthogonal decaging, Targeted drug delivery

Abstract

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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Published

2018-11-30

Issue

Section

Scientific Articles

How to Cite

[1]
S. Davies, B. J. Stenton, G. J. L. Bernardes, Chimia 2018, 72, 771, DOI: 10.2533/chimia.2018.771.