Repository logo
 

Tetrazine-Triggered Release of Carboxylic-Acid-Containing Molecules for Activation of an Anti-inflammatory Drug.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Qiao, Luxi 
Oliveira, Bruno L 
Navo, Claudio D 
Jiménez-Osés, Gonzalo 

Abstract

In addition to its use for the study of biomolecules in living systems, bioorthogonal chemistry has emerged as a promising strategy to enable protein or drug activation in a spatially and temporally controlled manner. This study demonstrates the application of a bioorthogonal inverse electron-demand Diels-Alder (iEDDA) reaction to cleave trans-cyclooctene (TCO) and vinyl protecting groups from carboxylic acid-containing molecules. The tetrazine-mediated decaging reaction proceeded under biocompatible conditions with fast reaction kinetics (<2 min). The anti-inflammatory activity of ketoprofen was successfully reinstated after decaging of the nontoxic TCOprodrug in live macrophages. Overall, this work expands the scope of functional groups and the application of decaging reactions to a new class of drugs.

Description

Keywords

anti-inflammatory drugs, bioorthogonal decaging, inverse electron-demand Diels-Alder reaction, tetrazine, trans-cyclooctene, Animals, Anti-Inflammatory Agents, Non-Steroidal, Carboxylic Acids, Cycloaddition Reaction, Fluorescent Dyes, Heterocyclic Compounds, Ketoprofen, Macrophages, Mice, RAW 264.7 Cells

Journal Title

Chembiochem

Conference Name

Journal ISSN

1439-4227
1439-7633

Volume Title

20

Publisher

Wiley
Sponsorship
EPSRC (1800475)
The Royal Society (uf110046)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (702574)
Royal Society (URF\R\180019)
European Research Council (676832)