Premium
Vinyl Ether/Tetrazine Pair for the Traceless Release of Alcohols in Cells
Author(s) -
JiménezMoreno Ester,
Guo Zijian,
Oliveira Bruno L.,
Albuquerque Inês S.,
Kitowski Annabel,
Guerreiro Ana,
Boutureira Omar,
Rodrigues Tiago,
JiménezOsés Gonzalo,
Bernardes Gonçalo J. L.
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201609607
Subject(s) - tetrazine , bioorthogonal chemistry , chemistry , vinyl ether , moiety , combinatorial chemistry , prodrug , reagent , ether , fluorophore , molecule , cleavage (geology) , protecting group , stereochemistry , organic chemistry , click chemistry , biochemistry , fluorescence , physics , quantum mechanics , copolymer , polymer , geotechnical engineering , alkyl , fracture (geology) , engineering
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.