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

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.

SUBMITTER: Jimenez-Moreno E

PROVIDER: S-EPMC6485351 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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

Jiménez-Moreno Ester E Guo Zijian Z Oliveira Bruno L BL Albuquerque Inês S IS Kitowski Annabel A Guerreiro Ana A Boutureira Omar O Rodrigues Tiago T Jiménez-Osés Gonzalo G Bernardes Gonçalo J L GJ

Angewandte Chemie (International ed. in English) 20161208 1

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-mediat ...[more]

PMID: 27930843

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