Dichloro Butenediamides as irreversible site‐selective protein conjugation reagent
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| Outros Autores: | , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/49943 |
Resumo: | © 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
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Dichloro Butenediamides as irreversible site‐selective protein conjugation reagentMichael additionBioconjugationCysteineIrreversibilityMaleimides© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.We describe maleic-acid derivatives as robust cysteine-selective reagents for protein labelling with comparable kinetics and superior stability relative to maleimides. Diamide and amido-ester derivatives proved to be efficient protein-labelling species with a common mechanism in which a spontaneous cyclization occurs upon addition to cysteine. Introduction of chlorine atoms in their structures triggers ring hydrolysis or further conjugation with adjacent residues, which results in conjugates that are completely resistant to retro-Michael reactions in the presence of biological thiols and human plasma. By controlling the microenvironment of the reactive site, we can control selectivity towards the hydrolytic pathway, forming homogeneous conjugates. The method is applicable to several scaffolds and enables conjugation of different payloads. The synthetic accessibility of these reagents and the mild conditions required for fast and complete conjugation together with the superior stability of the conjugates make this strategy an important alternative to maleimides in bioconjugation.This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement N° 836698 and under grant agreement N° 852985. Funding from the Scripps Research Institute (A.A.), FCT Portugal (PhD scholarship PD/BD/135512/2018 to C.F.A. and FCT Stimulus CEECIND/00453/2018 to G.J.L.B.) and Agencia Estatal Investigación of Spain (AEI; Grant RTI2018-099592-B-C21 to F.C.) is also acknowledged.John Wiley & Sons, Inc.Repositório da Universidade de LisboaLaserna, VictorAbegg, DanielAfonso, Cláudia F.Martin, Esther M.Adibekian, AlexanderRavn, PeterCorzana, FranciscoBernardes, Gonçalo J. L.2021-10-19T13:35:24Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/49943engAngew Chem Int Ed Engl. 2021 Oct 25;60(44):23750-237551433-785110.1002/anie.2021087911521-3773info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:53:56Zoai:repositorio.ul.pt:10451/49943Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:01:28.743892Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Dichloro Butenediamides as irreversible site‐selective protein conjugation reagent |
| title |
Dichloro Butenediamides as irreversible site‐selective protein conjugation reagent |
| spellingShingle |
Dichloro Butenediamides as irreversible site‐selective protein conjugation reagent Laserna, Victor Michael addition Bioconjugation Cysteine Irreversibility Maleimides |
| title_short |
Dichloro Butenediamides as irreversible site‐selective protein conjugation reagent |
| title_full |
Dichloro Butenediamides as irreversible site‐selective protein conjugation reagent |
| title_fullStr |
Dichloro Butenediamides as irreversible site‐selective protein conjugation reagent |
| title_full_unstemmed |
Dichloro Butenediamides as irreversible site‐selective protein conjugation reagent |
| title_sort |
Dichloro Butenediamides as irreversible site‐selective protein conjugation reagent |
| author |
Laserna, Victor |
| author_facet |
Laserna, Victor Abegg, Daniel Afonso, Cláudia F. Martin, Esther M. Adibekian, Alexander Ravn, Peter Corzana, Francisco Bernardes, Gonçalo J. L. |
| author_role |
author |
| author2 |
Abegg, Daniel Afonso, Cláudia F. Martin, Esther M. Adibekian, Alexander Ravn, Peter Corzana, Francisco Bernardes, Gonçalo J. L. |
| author2_role |
author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Laserna, Victor Abegg, Daniel Afonso, Cláudia F. Martin, Esther M. Adibekian, Alexander Ravn, Peter Corzana, Francisco Bernardes, Gonçalo J. L. |
| dc.subject.por.fl_str_mv |
Michael addition Bioconjugation Cysteine Irreversibility Maleimides |
| topic |
Michael addition Bioconjugation Cysteine Irreversibility Maleimides |
| description |
© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021-10-19T13:35:24Z 2021 2021-01-01T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/49943 |
| url |
http://hdl.handle.net/10451/49943 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Angew Chem Int Ed Engl. 2021 Oct 25;60(44):23750-23755 1433-7851 10.1002/anie.202108791 1521-3773 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
John Wiley & Sons, Inc. |
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John Wiley & Sons, Inc. |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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