- Stable Pyrrole-Linked Bioconjugates through Tetrazine-Triggered Azanorbornadiene Fragmentation
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An azanorbornadiene bromovinyl sulfone reagent for cysteine-selective bioconjugation has been developed. Subsequent reaction with dipyridyl tetrazine leads to bond cleavage and formation of a pyrrole-linked conjugate. The latter involves ligation of the tetrazine to the azanorbornadiene-tagged protein through inverse electron demand Diels–Alder cycloaddition with subsequent double retro-Diels–Alder reactions to form a stable pyrrole linkage. The sequence of site-selective bioconjugation followed by bioorthogonal bond cleavage was efficiently employed for the labelling of three different proteins. This method benefits from easy preparation of these reagents, selectivity for cysteine, and stability after reaction with a commercial tetrazine, which has potential for the routine preparation of protein conjugates for chemical biology studies.
- Bernardes, Gon?alo J. L.,Corzana, Francisco,Gil de Montes, Enrique,Hoyt, Emily A.,Istrate, Alena,Jiménez-Moreno, Ester,Jiménez-Osés, Gonzalo,Moreno-Vargas, Antonio J.,Navo, Claudio D.,Robina, Inmaculada
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supporting information
p. 6196 - 6200
(2020/02/25)
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- Vinylboronic acid-caged prodrug activation using click-to-release tetrazine ligation
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Bioorthogonal reactions can be performed selectively in the presence of any biological functional group and are widely used to achieve site-selective chemical modifications of biomolecules. The click-to-release reaction is a bioorthogonal bond-cleavage variant that has gained much interest over the last few years. The bioorthogonal reaction between tetrazines and trans-cyclooctenes or vinyl ethers, for example, initiates the release of a small molecule immediately after the cycloaddition with tetrazines. Recently, our group reported that vinylboronic acids (VBAs) give exceptionally high reaction rates in the bioorthogonal inverse electron-demand Diels-Alder reaction with tetrazines that are substituted with boron-coordinating ligands. In the present study, we show that VBAs can be used in a click-to-release variant and demonstrate its bioorthogonality with a VBA-protected doxorubicin prodrug. We show that the cytotoxicity of doxorubicin is silenced by the attachment of the VBA, and activity can be largely restored upon the reaction with a tetrazine, inducing cell death.
- Lelieveldt, Lianne P.W.M.,Eising, Selma,Wijen, Abel,Bonger, Kimberly M.
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supporting information
p. 8816 - 8821
(2019/10/22)
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- Vinyl Ether/Tetrazine Pair for the Traceless Release of Alcohols in Cells
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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.
- Jiménez-Moreno, Ester,Guo, Zijian,Oliveira, Bruno L.,Albuquerque, Inês S.,Kitowski, Annabel,Guerreiro, Ana,Boutureira, Omar,Rodrigues, Tiago,Jiménez-Osés, Gonzalo,Bernardes, Gon?alo J. L.
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supporting information
p. 243 - 247
(2016/12/30)
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- Inverse electron demand Diels-Alder (iEDDA) functionalisation of macroporous poly(dicyclopentadiene) foams
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Inverse electron demand Diels-Alder reactions performed on the double bonds in open cellular macroporous poly(dicyclopentadiene) monoliths yield a high degree of functionalisation (up to 2 mmol pyridazines per g or 8 mmol N per g) with grafted di(pyridyl)pyridazines in a single step.
- Knall, Astrid-Caroline,Kovacic, Sebastijan,Hollauf, Manuel,Reishofer, David,Saf, Robert,Slugovc, Christian
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supporting information
p. 7325 - 7327
(2013/09/23)
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- Thermal generation of pentacenes from soluble 6,13-dihydro-6,13- ethenopentacene precursors by a Diels-Alder-retro-Diels-Alder sequence with 3,6-disubstituted tetrazines
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3,6-Substituted tetrazines 2 (a: R2 = 2-pyridyl or b: CO 2Me) react with 2,3,9,10-(R1)4-dihydro-6,13- ethenopentacene 3 in solution at elevated temperature to the corresponding pentacene 1 (a: R1 = H, b: OBn, c: F).
- Bula, Rafael P.,Oppel, Iris M.,Bettinger, Holger F.
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experimental part
p. 3538 - 3542
(2012/06/15)
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- Regiospecific fragmentation of benzene derivatives: Synthetic and analytical applications
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The cycloadducts formed from arenes and tetrachloro- and tetrafluorobenzyne have been shown to undergo specific addition-fragmentation reactions. These sequences are both simple syntheses of arenes with unusual substitution patterns and a convenient alternative to the other methods currently available for assaying the isotopic distribution in [14C]-labelled benzene derivatives.
- Hales, Neil J.,Heaney, Harry,Hollinshead, John H.,Ley, Steven V.
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p. 7755 - 7776
(2007/10/02)
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