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

Jiménez-Moreno, E. ; Guo, Z. ; Oliveira, B.L. ; Albuquerque, I.S. ; Kitowski, A. ; Guerreiro, A. ; Boutureira, O. ; Rodrigues, T. ; Jiménez-Osés, G. ; Bernardes, G.J.L.

Resumen: 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.

Idioma: Inglés

DOI: 10.1002/anie.201609607

Año: 2017

Publicado en: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 56, 1 (2017), 243-247
ISSN: 1433-7851

Factor impacto JCR: 12.102 (2017)

Categ. JCR: CHEMISTRY, MULTIDISCIPLINARY rank: 14 / 171 = 0.082 (2017) - Q1 - T1

Factor impacto SCIMAGO: 6.155 - Chemistry (miscellaneous) (Q1) - Catalysis (Q1)

Financiación: info:eu-repo/grantAgreement/ES/MICINN/RYC-2013-14706
Financiación: info:eu-repo/grantAgreement/ES/MINECO/CTQ2015-70524-R

Tipo y forma: Article (Published version)