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Vinyl Ether/Tetrazine Pair for the Traceless Release of Alcohols in Cells

Published version
Peer-reviewed

Type

Article

Change log

Authors

Jiménez-Moreno, E 
Guo, Z 
Oliveira, BL 
Albuquerque, IS 
Kitowski, A 

Abstract

The cleavage of a protecting group from a protein or drug under bioorthogonal conditions enables accurate spatiotemporal control over protein or drug activity. Disclosed herein is that vinyl ethers serve as protecting groups for alcohol-containing molecules and as reagents for bioorthogonal bond-cleavage reactions. A vinyl ether moiety was installed in a range of molecules, including amino acids, a monosaccharide, a fluorophore, and an analogue of the cytotoxic drug duocarmycin. Tetrazine-mediated decaging proceeded under biocompatible conditions with good yields and reasonable kinetics. Importantly, the nontoxic, vinyl ether duocarmycin double prodrug was successfully decaged in live cells to reinstate cytotoxicity. This bioorthogonal reaction presents broad applicability and may be suitable for in vivo applications.

Description

Keywords

caged compounds, drug delivery, ethers, fluorescent probes, heterocycles

Journal Title

Angewandte Chemie - International Edition

Conference Name

Journal ISSN

1433-7851
1521-3773

Volume Title

56

Publisher

John Wiley & Sons Ltd.
Sponsorship
Engineering and Physical Sciences Research Council (EP/M003647/1)
European Research Council (676832)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (702574)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (701473)
European Commission (EC) (852985)
European Commission; China Scholarship Council; FCT Portugal; MINECO (CTQ2015-70524-R and RYC-2013-14706); EPSRC; Royal Society; European Research Council (TagIt)