title: 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.
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW, Cambridge, UK.
authors.forename: Ester
authors.initials: E
authors.lastname: Jiménez-Moreno
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW, Cambridge, UK.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW, Cambridge, UK.
authors.forename: Bruno L
authors.initials: BL
authors.lastname: Oliveira
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal.
authors.forename: Inês S
authors.initials: IS
authors.lastname: Albuquerque
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal.
authors.forename: Annabel
authors.initials: A
authors.lastname: Kitowski
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Guerreiro
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW, Cambridge, UK.
authors.forename: Omar
authors.initials: O
authors.lastname: Boutureira
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal.
authors.forename: Tiago
authors.initials: T
authors.lastname: Rodrigues
authors.affiliation: Departamento de Química, Universidad de La Rioja, Centro de Investigación en Síntesis Química, 26006, Logroño, Spain.|Institute of Biocomputation and Physics of Complex Systems (BIFI), University of Zaragoza, BIFI-IQFR (CSIC), Zaragoza, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Jiménez-Osés
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW, Cambridge, UK.|Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal.
authors.forename: Gonçalo J L
authors.identifier: 0000-0001-6594-8917
authors.initials: GJ
authors.lastname: Bernardes
mesh_terms: D000438:Alcohols / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D061565:Cycloaddition Reaction; D004583:Electrons; D056945:Hep G2 Cells; D006801:Humans; D007700:Kinetics; D015394:Molecular Structure; D011789:Quantum Theory; D013777:Tetrazoles / Q000737:chemistry / Q000378:metabolism*; D014753:Vinyl Compounds / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000438:Alcohols; D013777:Tetrazoles; D014753:Vinyl Compounds; C100195:vinyl ether
keywords: caged compounds; drug delivery; ethers; fluorescent probes; heterocycles