Publicação
Quaternization of Vinyl/Alkynyl Pyridine enables ultrafast cysteine‐selective protein modification and charge modulation
| 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. |
|---|---|
| Autores principais: | Matos, Maria J. |
| 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. |
| Assunto: | Antibody-drug conjugates Bioconjugation Cysteine Microfluidics Protein modification |
| Ano: | 2019 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| _version_ | 1866810814516690944 |
|---|---|
| author | Matos, Maria J. |
| 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 |
| 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 |
| contributor_name_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Matos, Maria J.\"},{\"Person.name\":\"Navo, Claudio D.\"},{\"Person.name\":\"Hakala, Tuuli\"},{\"Person.name\":\"Ferhati, Xhenti\"},{\"Person.name\":\"Guerreiro, Ana\",\"Person.identifier.orcid\":\"0000-0002-2173-6514\"},{\"Person.name\":\"Hartmann, David\"},{\"Person.name\":\"Bernardim, Barbara\"},{\"Person.name\":\"Saar, Kadi L.\"},{\"Person.name\":\"Compañón, Ismael\"},{\"Person.name\":\"Corzana, Francisco\"},{\"Person.name\":\"Knowles, Tuomas P. J.\"},{\"Person.name\":\"Jiménez‐Osés, Gonzalo\"},{\"Person.name\":\"Bernardes, Gonçalo J. L.\",\"Person.identifier.orcid\":\"0000-0001-6594-8917\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| datacite.creators.creator.creatorName.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. |
| datacite.date.Accepted.fl_str_mv | 2019-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2022-05-10T14:18:55Z |
| datacite.date.embargoed.fl_str_mv | 2022-05-10T14:18:55Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Antibody-drug conjugates Bioconjugation Cysteine Microfluidics Protein modification |
| datacite.titles.title.fl_str_mv | Quaternization of Vinyl/Alkynyl Pyridine enables ultrafast cysteine‐selective protein modification and charge modulation |
| dc.contributor.none.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| dc.creator.none.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.date.Accepted.fl_str_mv | 2019-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2022-05-10T14:18:55Z |
| dc.date.embargoed.fl_str_mv | 2022-05-10T14:18:55Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10451/52854 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Wiley |
| dc.rights.cclincense.fl_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Antibody-drug conjugates Bioconjugation Cysteine Microfluidics Protein modification |
| dc.title.fl_str_mv | Quaternization of Vinyl/Alkynyl Pyridine enables ultrafast cysteine‐selective protein modification and charge modulation |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | 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. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorio.ulisboa.pt/bitstreams/582af365-5247-4829-be4e-673f8d9f3c7e/download |
| funding.funder.alternateName_str_mv | FCT FCT |
| funding.funder.identifier_str_mv | http://doi.org/10.13039/501100001871 http://doi.org/10.13039/501100001871 |
| funding.funder.name_str_mv | Fundação para a Ciência e a Tecnologia Fundação para a Ciência e a Tecnologia |
| funding.name_str_mv | Investigador FCT OE |
| id | ul_09814019dbc0fe12e133d8a63beffbb7 |
| identifier.url.fl_str_mv | http://hdl.handle.net/10451/52854 |
| instacron_str | ul |
| institution | Universidade de Lisboa |
| instname_str | Universidade de Lisboa |
| language | eng |
| network_acronym_str | ul |
| network_name_str | Repositório da Universidade de Lisboa |
| oai_identifier_str | oai:repositorio.ulisboa.pt:10451/52854 |
| organization_str_mv | urn:organizationAcronym:ul |
| person_str_mv | Matos, Maria J. Navo, Claudio D. Hakala, Tuuli Ferhati, Xhenti Guerreiro, Ana Guerreiro, Ana https://www.ciencia-id.pt/481C-A494-B69D 481C-A494-B69D http://orcid.org/0000-0002-2173-6514 0000-0002-2173-6514 Hartmann, David Bernardim, Barbara Saar, Kadi L. Compañón, Ismael Corzana, Francisco Knowles, Tuomas P. J. Jiménez‐Osés, Gonzalo Bernardes, Gonçalo J. L. Bernardes, Gonçalo J. L. http://orcid.org/0000-0001-6594-8917 0000-0001-6594-8917 |
| publishDate | 2019 |
| publisher.none.fl_str_mv | Wiley |
| reponame_str | Repositório da Universidade de Lisboa |
| repository_id_str | urn:repositoryAcronym:ul |
| service_str_mv | urn:repositoryAcronym:ul |
| spelling | engWileypt_PTQuaternized 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.application/pdfpt_PTQuaternization of Vinyl/Alkynyl Pyridine enables ultrafast cysteine‐selective protein modification and charge modulationMatos, Maria J.Navo, Claudio D.Hakala, TuuliFerhati, XhentiPersonalGuerreiro, AnaDSpacehttp://dspace.org/items/1c4166db-cf53-48ab-9e3f-476f142cb304DSpacehttp://dspace.org/items/1c4166db-cf53-48ab-9e3f-476f142cb304dos Santos GuerreiroAna MariaCiência IDhttps://www.ciencia-id.pt481C-A494-B69DORCIDhttp://orcid.org0000-0002-2173-6514Hartmann, DavidBernardim, BarbaraSaar, Kadi L.Compañón, IsmaelCorzana, FranciscoKnowles, Tuomas P. J.Jiménez‐Osés, GonzaloPersonalBernardes, Gonçalo J. L.DSpacehttp://dspace.org/items/d1a48067-77b1-4413-b1c7-602fb18c62c0DSpacehttp://dspace.org/items/d1a48067-77b1-4413-b1c7-602fb18c62c0BernardesGonçaloORCIDhttp://orcid.org0000-0001-6594-8917Scopus Author IDhttps://www.scopus.com14046757500HostingInstitutionOrganizationalRepositório Científico de Acesso Aberto da ULisboae-mailmailto:repositorio@reitoria.ulisboa.ptrepositorio@reitoria.ulisboa.ptISSNIsPartOf1433-7851DOIIsPartOf10.1002/anie.2019014052022-05-10T14:18:55Z20192019-01-01T00:00:00ZHandlehttp://hdl.handle.net/10451/52854http://purl.org/coar/access_right/c_abf2open accessAntibody-drug conjugatesBioconjugationCysteineMicrofluidicsProtein modification2062491 bytesFundação para a Ciência e a TecnologiaModulation and targeting of calcium channels with ligand-drug conjugates for cancer therapyInvestigador FCTCrossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a TecnologiaSynthetically-defined glycoconjugate vaccine candidates against InfluenzaOECrossref Funder IDhttp://doi.org/10.13039/501100001871literaturehttp://purl.org/coar/resource_type/c_6501journal article2019http://creativecommons.org/licenses/by/4.0/http://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorio.ulisboa.pt/bitstreams/582af365-5247-4829-be4e-673f8d9f3c7e/downloadAngewandte Chemie International Edition582066406644 |
| 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 |
| status | SINGLETON |
| subject.fl_str_mv | Antibody-drug conjugates Bioconjugation Cysteine Microfluidics Protein modification |
| title | 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_short | 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 |
| topic | Antibody-drug conjugates Bioconjugation Cysteine Microfluidics Protein modification |
| topic_facet | Antibody-drug conjugates Bioconjugation Cysteine Microfluidics Protein modification |
| url | http://hdl.handle.net/10451/52854 |
| visible | 1 |