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

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-cle...

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Detalles Bibliográficos
Autores: Jiménez-Moreno, E. [0000-0002-5045-433X], Guo, Z., Oliveira, B.L. [0000-0002-7687-4746], Albuquerque, I.S. [0000-0002-1108-0961], Kitowski, A., Guerreiro, A., Boutureira, O. [0000-0002-0768-8309], Rodrigues, T. [0000-0002-0973-9763], Jiménez-Osés, G. [0000-0003-0105-4337], Bernardes, G.J.L. [0000-0001-6594-8917]
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Universidad de La Rioja (UR)
Repositorio:RIUR. Repositorio Institucional de la Universidad de La Rioja
OAI Identifier:oai:portal.dialnet.es:doc/5bbc6932b750603269e816f2
Acceso en línea:https://investigacion.unirioja.es/documentos/5bbc6932b750603269e816f2
Access Level:acceso abierto
Palabra clave:caged compounds
drug delivery
ethers
fluorescent probes
heterocycles
Descripción
Sumario: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. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.