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Iminoboronates are efficient intermediates for selective, rapid and reversible N-terminal cysteine functionalisation

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dc.contributor.authorFaustino, Hélio
dc.contributor.authorSilva, Maria J. S. A.
dc.contributor.authorVeiros, Luis Filipe
dc.contributor.authorBernardes, Gonçalo J. L.
dc.contributor.authorGois, Pedro M. P.
dc.date.accessioned2022-06-14T15:38:56Z
dc.date.available2022-06-14T15:38:56Z
dc.date.issued2016
dc.descriptionThis journal is © The Royal Society of Chemistry 2016. This article is licensed under a Creative Commons Attribution 3.0 Unported Licencept_PT
dc.description.abstractWe show that formyl benzeno boronic acids (2FBBA) selectively react with N-terminal cysteines to yield a boronated thiazolidine featuring a B-N bond. The reaction exhibits a very rapid constant rate (2.38 ± 0.23 × 102 M-1 s-1) under mild aqueous conditions (pH 7.4, 23 °C) and tolerates different amino acids at the position adjacent to the N-cysteine. DFT calculations highlighted the diastereoselective nature of this ligation reaction and support the involvement of the proximal boronic acid in the activation of the imine functionality and the stabilisation of the boronated thiazolidine through a chelate effect. The 2FBBA reagent allowed the effective functionalisation of model peptides (C-ovalbumin and a laminin fragment) and the boronated thiazolidine construct was shown to be stable over time, though the reaction was reversible in the presence of benzyl hydroxylamine. The reaction proved to be highly chemoselective, and 2FBBA was used to functionalize the N-terminal cysteine of calcitonin in the presence of a potentially competing in-chain thiol group. This exquisite selectivity profile enabled the dual functionalisation of calcitonin and the interactive orthogonal modification of this peptide when 2FBBA was combined with conventional maleimide chemistry. These results highlight the potential of this methodology to construct complex and well-defined bioconjugates.pt_PT
dc.description.sponsorshipWe acknowledge the financial support of Fundação para a Ciência e a Tecnologia (FCT) Portugal (grants SFRH/BPD/102296/2014, PTDC/QEQMED/5512/2014, PTDC/QEQ-QOR/1434/2014; P. M. P. Gois and G. J. L. Bernardes are FCT Investigators; iMed.ULisboa grant UID/DTP/04138/2013) and the EU (Marie-Sklodowska Curie ITN ProteinConjugates). L. F. V. acknowledges Fundação para a Ciência e Tecnologia, UID/QUI/00100/2013. G. J. L. B. is a Royal Society University Research Fellow.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationChem Sci. 2016 Aug 1;7(8):5052-5058pt_PT
dc.identifier.doi10.1039/C6SC01520Dpt_PT
dc.identifier.eissn2041-6539
dc.identifier.issn2041-6520
dc.identifier.urihttp://hdl.handle.net/10451/53379
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherRoyal Society of Chemistrypt_PT
dc.relationPTDC/QEQMED/5512/2014pt_PT
dc.relationDesign of iminoboronate based antitumor targeting conjugates
dc.relationResearch Institute for Medicines
dc.relationCentro de Química Estrutural
dc.relation.publisherversionhttps://pubs.rsc.org/en/journals/journalissues/sc#!recentarticles&advpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleIminoboronates are efficient intermediates for selective, rapid and reversible N-terminal cysteine functionalisationpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberSFRH/BPD/102296/2014
oaire.awardNumberPTDC/QEQ-QOR/1434/2014
oaire.awardNumberUID/DTP/04138/2013
oaire.awardNumberUID/QUI/00100/2013
oaire.awardTitleDesign of iminoboronate based antitumor targeting conjugates
oaire.awardTitleResearch Institute for Medicines
oaire.awardTitleCentro de Química Estrutural
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBPD%2F102296%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FQEQ-QOR%2F1434%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FDTP%2F04138%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FQUI%2F00100%2F2013/PT
oaire.citation.endPage5058pt_PT
oaire.citation.issue8pt_PT
oaire.citation.startPage5052pt_PT
oaire.citation.titleChemical Sciencept_PT
oaire.citation.volume7pt_PT
oaire.fundingStreamOE
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
person.familyNameFerreira Faustino
person.familyNameSilva
person.familyNameVeiros
person.familyNameBernardes
person.familyNameGois
person.givenNameHélio Manuel
person.givenNameMaria J.S.A.
person.givenNameLuis Filipe
person.givenNameGonçalo
person.givenNamePedro
person.identifierE-1903-2012
person.identifier.ciencia-idAC1F-A27B-0CD7
person.identifier.ciencia-idF41A-9D1E-748D
person.identifier.ciencia-id4811-005D-5B7F
person.identifier.ciencia-idAD1B-6A14-C952
person.identifier.orcid0000-0002-0378-3624
person.identifier.orcid0000-0003-4178-1942
person.identifier.orcid0000-0001-5841-3519
person.identifier.orcid0000-0001-6594-8917
person.identifier.orcid0000-0002-7698-630X
person.identifier.ridE-8208-2017
person.identifier.ridA-9251-2014
person.identifier.scopus-author-id25121396900
person.identifier.scopus-author-id57198412711
person.identifier.scopus-author-id6701545795
person.identifier.scopus-author-id14046757500
person.identifier.scopus-author-id6507726637
project.funder.identifierhttp://doi.org/10.13039/501100001871
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project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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