Detalhes bibliográficos
| Resumo: | 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. |
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| Autores principais: | Matos, Maria J. |
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| Outros Autores: | 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. |
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| Assunto: | Antibody-drug conjugates Bioconjugation Cysteine Microfluidics Protein modification |
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| Ano: | 2019 |
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| País: | Portugal |
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| Tipo de documento: | artigo |
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| Tipo de acesso: | acesso aberto |
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| Instituição associada: | Universidade de Lisboa |
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| Idioma: | inglês |
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| Origem: | Repositório da Universidade de Lisboa |
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