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Site-specific chemical modification of antibody fragments using traceless cleavable linkers

dc.contributor.authorBernardes, Gonçalo J. L.
dc.contributor.authorSteiner, Martina
dc.contributor.authorHartmann, Isabelle
dc.contributor.authorNeri, Dario
dc.contributor.authorCasi, Giulio
dc.date.accessioned2021-12-21T16:41:46Z
dc.date.available2021-12-21T16:41:46Z
dc.date.issued2013
dc.description© 2013 Nature America, Inc. All rights reserved.pt_PT
dc.description.abstractAntibody-drug conjugates (ADCs) are promising agents for the selective delivery of cytotoxic drugs to specific cells (for example, tumors). In this protocol, we describe two strategies for the precise modification at engineered C- or N-terminal cysteines of antibodies in IgG, diabody and small immunoprotein (SIP) formats that yield homogenous ADCs. In this protocol, cemadotin derivatives are used as model drugs, as these agents have a potent cytotoxic activity and are easy to synthesize. However, other drugs with similar functional groups could be considered. In the first approach, a cemadotin derivative containing a sulfhydryl group results in a mixed disulfide linkage. In the second approach, a cemadotin derivative containing an aldehyde group is joined via a thiazolidine linkage. The procedures outlined are robust, enabling the preparation of ADCs with a defined number of drugs per antibody in a time frame between 7 and 24 h.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationNat Protoc. 2013 Nov;8(11):2079-2089pt_PT
dc.identifier.doi10.1038/nprot.2013.121pt_PT
dc.identifier.eissn1750-2799
dc.identifier.issn1754-2189
dc.identifier.urihttp://hdl.handle.net/10451/50506
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Naturept_PT
dc.relation.publisherversionhttps://www.nature.com/nprot/pt_PT
dc.titleSite-specific chemical modification of antibody fragments using traceless cleavable linkerspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage2089pt_PT
oaire.citation.issue11pt_PT
oaire.citation.startPage2079pt_PT
oaire.citation.titleNature Protocolspt_PT
oaire.citation.volume8pt_PT
person.familyNameBernardes
person.givenNameGonçalo
person.identifier.orcid0000-0001-6594-8917
person.identifier.scopus-author-id14046757500
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationd1a48067-77b1-4413-b1c7-602fb18c62c0
relation.isAuthorOfPublication.latestForDiscoveryd1a48067-77b1-4413-b1c7-602fb18c62c0

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