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dc.contributor.authorSun, Shuangen
dc.contributor.authorAkkapeddi, Padmaen
dc.contributor.authorMarques, Marta Cen
dc.contributor.authorMartínez-Sáez, Nuriaen
dc.contributor.authorTorres, Vukosava Men
dc.contributor.authorCordeiro, Carlosen
dc.contributor.authorBoutureira, Omaren
dc.contributor.authorLopes Bernardes, Goncaloen
dc.date.accessioned2018-12-22T00:31:52Z
dc.date.available2018-12-22T00:31:52Z
dc.date.issued2019-02en
dc.identifier.issn1477-0520
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287420
dc.description.abstractMonoclonal antibodies have emerged as an important class of therapeutics in oncological and autoimmune diseases due to several attractive properties, such as high binding affinity and specificity. However, it has recently become clear that antibodies recovered from serum show significantly decreased potency owing to various reasons, including deamidation, oxidation, fragment antigen binding (Fab) exchange, and disulfide shuffling. Fab exchange and disulfide shuffling result because of the instability of disulfides in serum. Herein, we reported a ‘one-pot’ stapling strategy using isobutylene motifs to stabilise the interchain disulfides of antibodies. This general method was applied to a Fab fragment of anti-HER2 antibody. The stapled Fab was completely stable in the presence of biological thiols. The approach was further applied to two different full-length IgG, trastuzumab and rituximab, under mild and biocompatible conditions. The binding affinity of the antibody was enhanced, relative to its native form, after being stapled. The stapled structure maintained its effectors functions and behaved similarly as its native form in vivo. This work provides a straightforward and scalable method for the stabilisation antibodies in various formats.
dc.format.mediumPrinten
dc.languageengen
dc.publisherRoyal Society of Chemistry (RSC)
dc.titleOne-pot stapling of interchain disulfides of antibodies using an isobutylene motif.en
dc.typeArticle
prism.endingPage2012
prism.issueIdentifier7en
prism.publicationDate2019en
prism.publicationNameOrganic & biomolecular chemistryen
prism.startingPage2005
prism.volume17en
dc.identifier.doi10.17863/CAM.34724
dcterms.dateAccepted2018-11-27en
rioxxterms.versionofrecord10.1039/c8ob02877jen
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-02en
dc.contributor.orcidSun, Shuang [0000-0002-4384-7338]
dc.contributor.orcidBoutureira, Omar [0000-0002-0768-8309]
dc.contributor.orcidBernardes, Goncalo [0000-0001-6594-8917]
dc.identifier.eissn1477-0539
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idEPSRC (EP/M003647/1)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (675007)
pubs.funder-project-idRoyal Society (URF\R\180019)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) ERC (676832)
pubs.funder-project-idRoyal Society (uf110046)
rioxxterms.freetoread.startdate2019-12-12


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