Quaternization of Vinyl/Alkynyl Pyridine enables ultrafast cysteine‐selective protein modification and charge modulation
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2019 |
| 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/10451/52854 |
Resumo: | © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. 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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Quaternization of Vinyl/Alkynyl Pyridine enables ultrafast cysteine‐selective protein modification and charge modulationAntibody-drug conjugatesBioconjugationCysteineMicrofluidicsProtein modification© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. 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.Quaternized vinyl- and alkynyl-pyridine reagents were shown to react in an ultrafast and selective manner with several cysteine-tagged proteins at near-stoichiometric quantities. We have demonstrated that this method can effectively create a homogenous antibody-drug conjugate that features a precise drug-to-antibody ratio of 2, which was stable in human plasma and retained its specificity towards Her2+ cells. Finally, the developed warhead introduces a +1 charge to the overall net charge of the protein, which enabled us to show that the electrophoretic mobility of the protein may be tuned through the simple attachment of a quaternized vinyl pyridinium reagent at the cysteine residues. We anticipate the generalized use of quaternized vinyl- and alkynyl-pyridine reagents not only for bioconjugation, but also as warheads for covalent inhibition and as tools to profile cysteine reactivity.Funded under the EU Horizon 2020 Programme, Marie Skłodowska-Curie ITN GA No. 675007, the Royal Society (UF110046 and URF\R\180019 to G.J.L.B.), FCT Portugal (iFCT IF/00624/2015 to G.J.L.B. and PhD studentship SFRH/BD/115932/2016 to A.G.), Xunta de Galicia (Galician Plan of research, innovation and growth 2011–2015, ED481B 2014/086-0 and ED481B 2018/007 to M.J.M.), D.G.I. MINECO/FEDER (grants CTQ2015-70524-R and RYC-2013–14706 to G.J.-O. and C.D.N and CTQ2015-67727-R to F.C.), Universidad de la Rioja (FPI PhD studentship to I.C.), FAPESP (BEPE 2015/07509-1 and 2017/13168-8 to B.B.), and by an ERC StG (GA No. 676832).WileyRepositório da Universidade de LisboaMatos, Maria J.Navo, Claudio D.Hakala, TuuliFerhati, XhentiGuerreiro, AnaHartmann, DavidBernardim, BarbaraSaar, Kadi L.Compañón, IsmaelCorzana, FranciscoKnowles, Tuomas P. J.Jiménez‐Osés, GonzaloBernardes, Gonçalo J. L.2022-05-10T14:18:55Z20192019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/52854engAngew Chem Int Ed Engl. 2019 May 13;58(20):6640-66441433-785110.1002/anie.2019014051521-3773info: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:RCAAP2023-11-08T16:58:17Zoai:repositorio.ul.pt:10451/52854Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:03:51.688170Repositório 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 |
Quaternization of Vinyl/Alkynyl Pyridine enables ultrafast cysteine‐selective protein modification and charge modulation |
| title |
Quaternization of Vinyl/Alkynyl Pyridine enables ultrafast cysteine‐selective protein modification and charge modulation |
| spellingShingle |
Quaternization of Vinyl/Alkynyl Pyridine enables ultrafast cysteine‐selective protein modification and charge modulation Matos, Maria J. Antibody-drug conjugates Bioconjugation Cysteine Microfluidics Protein modification |
| title_short |
Quaternization of Vinyl/Alkynyl Pyridine enables ultrafast cysteine‐selective protein modification and charge modulation |
| title_full |
Quaternization of Vinyl/Alkynyl Pyridine enables ultrafast cysteine‐selective protein modification and charge modulation |
| title_fullStr |
Quaternization of Vinyl/Alkynyl Pyridine enables ultrafast cysteine‐selective protein modification and charge modulation |
| title_full_unstemmed |
Quaternization of Vinyl/Alkynyl Pyridine enables ultrafast cysteine‐selective protein modification and charge modulation |
| title_sort |
Quaternization of Vinyl/Alkynyl Pyridine enables ultrafast cysteine‐selective protein modification and charge modulation |
| author |
Matos, Maria J. |
| author_facet |
Matos, Maria J. Navo, Claudio D. Hakala, Tuuli Ferhati, Xhenti Guerreiro, Ana Hartmann, David Bernardim, Barbara Saar, Kadi L. Compañón, Ismael Corzana, Francisco Knowles, Tuomas P. J. Jiménez‐Osés, Gonzalo Bernardes, Gonçalo J. L. |
| author_role |
author |
| author2 |
Navo, Claudio D. Hakala, Tuuli Ferhati, Xhenti Guerreiro, Ana Hartmann, David Bernardim, Barbara Saar, Kadi L. Compañón, Ismael Corzana, Francisco Knowles, Tuomas P. J. Jiménez‐Osés, Gonzalo Bernardes, Gonçalo J. L. |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Matos, Maria J. Navo, Claudio D. Hakala, Tuuli Ferhati, Xhenti Guerreiro, Ana Hartmann, David Bernardim, Barbara Saar, Kadi L. Compañón, Ismael Corzana, Francisco Knowles, Tuomas P. J. Jiménez‐Osés, Gonzalo Bernardes, Gonçalo J. L. |
| dc.subject.por.fl_str_mv |
Antibody-drug conjugates Bioconjugation Cysteine Microfluidics Protein modification |
| topic |
Antibody-drug conjugates Bioconjugation Cysteine Microfluidics Protein modification |
| description |
© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. 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 |
2019 |
| dc.date.none.fl_str_mv |
2019 2019-01-01T00:00:00Z 2022-05-10T14:18:55Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10451/52854 |
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http://hdl.handle.net/10451/52854 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Angew Chem Int Ed Engl. 2019 May 13;58(20):6640-6644 1433-7851 10.1002/anie.201901405 1521-3773 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Wiley |
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Wiley |
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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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