Stable Pyrrole-Linked Bioconjugates through Tetrazine-Triggered Azanorbornadiene Fragmentation
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 prote...
| Autores: | , , , , , , , , , |
|---|---|
| Tipo de documento: | artigo |
| Estado: | Versão publicada |
| Data de publicação: | 2020 |
| País: | España |
| Recursos: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositório: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/344461 |
| Acesso em linha: | http://hdl.handle.net/10261/344461 |
| Access Level: | Acceso aberto |
| Palavra-chave: | bioconjugation chemical biology cycloaddition heterocycles proteins |
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Stable Pyrrole-Linked Bioconjugates through Tetrazine-Triggered Azanorbornadiene FragmentationGil de Montes, EnriqueIstrate, AlenaNavo, Claudio D.Jiménez-Moreno, EsterHoyt, Emily A.Corzana, FranciscoRobina, InmaculadaJiménez-Osés, GonzaloMoreno-Vargas, Antonio J.Bernardes, Gonçalo J. L.bioconjugationchemical biologycycloadditionheterocyclesproteinsAn 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.We thank the Spanish Ministry of Education, Culture and Sport under the FPU program (E.G.M.), the Spanish Ministry of Economy and Competitiveness (CTQ2016-77270-R toA.J.M.-V., E.G.M. and I.R., RTI2018-099592-B-C22 andRYC-2013–14706 to G.J.-O. and RTI2018-099592-B-C21 toF.C.), the EU (Marie-Sklodowska Curie Actions to E.J.M.,GA No. 701473), and FCT Portugal (FCT Investigator toG.J.L.B., IF/00624/2015) for funding. We thank Dr. AndrØNeves and Prof. Kevin Brindle (CRUK Cambridge Institute,UK) for providing the C2Am protein; Dr. S. Massa and Prof.N. Devoogdt (Vrije Universiteit Brussel, Brussels) for thegenerous gift of the HER2-targeting nanobody 2Rb17c, and Dr. Vikki Cantrill for her help with the preparation andediting of this manuscript. We also thank CITIUS for NMRand mass spectrometry assistance and BERONIA (Universidad de La Rioja) for computer support. G.J.L.B. is a Royal Society University Research Fellow (URF\R\180019) recip-ient of a European Research Council Starting Grant (TagIt,GA. 676832).Peer reviewedWiley-VCHMinisterio de Educación, Cultura y Deporte (España)Ministerio de Economía y Competitividad (España)University of CambridgeUniversidad de La RiojaEuropean Commission202420242020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/344461reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-099592-B-C22info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-099592-B-C21info:eu-repo/grantAgreement/EC/HE/676832https://doi.org/10.1002/anie.201914529Noinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3444612026-05-22T06:33:51Z |
| dc.title.none.fl_str_mv |
Stable Pyrrole-Linked Bioconjugates through Tetrazine-Triggered Azanorbornadiene Fragmentation |
| title |
Stable Pyrrole-Linked Bioconjugates through Tetrazine-Triggered Azanorbornadiene Fragmentation |
| spellingShingle |
Stable Pyrrole-Linked Bioconjugates through Tetrazine-Triggered Azanorbornadiene Fragmentation Gil de Montes, Enrique bioconjugation chemical biology cycloaddition heterocycles proteins |
| title_short |
Stable Pyrrole-Linked Bioconjugates through Tetrazine-Triggered Azanorbornadiene Fragmentation |
| title_full |
Stable Pyrrole-Linked Bioconjugates through Tetrazine-Triggered Azanorbornadiene Fragmentation |
| title_fullStr |
Stable Pyrrole-Linked Bioconjugates through Tetrazine-Triggered Azanorbornadiene Fragmentation |
| title_full_unstemmed |
Stable Pyrrole-Linked Bioconjugates through Tetrazine-Triggered Azanorbornadiene Fragmentation |
| title_sort |
Stable Pyrrole-Linked Bioconjugates through Tetrazine-Triggered Azanorbornadiene Fragmentation |
| dc.creator.none.fl_str_mv |
Gil de Montes, Enrique Istrate, Alena Navo, Claudio D. Jiménez-Moreno, Ester Hoyt, Emily A. Corzana, Francisco Robina, Inmaculada Jiménez-Osés, Gonzalo Moreno-Vargas, Antonio J. Bernardes, Gonçalo J. L. |
| author |
Gil de Montes, Enrique |
| author_facet |
Gil de Montes, Enrique Istrate, Alena Navo, Claudio D. Jiménez-Moreno, Ester Hoyt, Emily A. Corzana, Francisco Robina, Inmaculada Jiménez-Osés, Gonzalo Moreno-Vargas, Antonio J. Bernardes, Gonçalo J. L. |
| author_role |
author |
| author2 |
Istrate, Alena Navo, Claudio D. Jiménez-Moreno, Ester Hoyt, Emily A. Corzana, Francisco Robina, Inmaculada Jiménez-Osés, Gonzalo Moreno-Vargas, Antonio J. Bernardes, Gonçalo J. L. |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Ministerio de Educación, Cultura y Deporte (España) Ministerio de Economía y Competitividad (España) University of Cambridge Universidad de La Rioja European Commission |
| dc.subject.none.fl_str_mv |
bioconjugation chemical biology cycloaddition heterocycles proteins |
| topic |
bioconjugation chemical biology cycloaddition heterocycles proteins |
| description |
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. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 2024 2024 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10261/344461 |
| url |
http://hdl.handle.net/10261/344461 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
#PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-099592-B-C22 info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-099592-B-C21 info:eu-repo/grantAgreement/EC/HE/676832 https://doi.org/10.1002/anie.201914529 No |
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info:eu-repo/semantics/openAccess |
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openAccess |
| dc.publisher.none.fl_str_mv |
Wiley-VCH |
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Wiley-VCH |
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reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
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Consejo Superior de Investigaciones Científicas (CSIC) |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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15,812429 |