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Peptibodies : an elegant solution for a long-standing problem

dc.contributor.authorCavaco, Marco
dc.contributor.authorCastanho, Miguel A. R. B.
dc.contributor.authorNeves, Vera
dc.date.accessioned2019-03-22T13:47:40Z
dc.date.available2019-03-22T13:47:40Z
dc.date.issued2018
dc.description© 2017 Wiley Periodicals, Inc.pt_PT
dc.description.abstractChimeric proteins composed of a biologically active peptide and a fragment crystallizable (Fc) domain of immunoglobulin G (IgG) are known as peptibodies. They present an extended half-life due to neonatal Fc receptor (FcRn) salvage pathway, a decreased renal clearance rate owing to its increased size (≈70 kDa) and, depending on the peptide used in the design of the peptibody, an active-targeting moiety. Also, the peptides therapeutic activity is boosted by the number of peptides in the fusion protein (at least two peptides) and to some peptides’ alterations. Peptibodies are mainly obtained through recombinant DNA technology. However, to improve peptide properties, “unnatural” changes have been introduced to the original peptides’ sequence, for instance, the incorporation of D- or non-natural amino acid residues or even cyclization thus, limiting the application of genetic engineering in the production of peptibodies, since these peptides must be obtained via chemical synthesis. This constrains prompted the development of new methods for conjugation of peptides to Fc domains. Another challenge, subject of intense research, relates to the large-scale production of such peptibodies using these new techniques, which can be minimized by their proved value. To date, two peptibodies, romiplostim and dulaglutide, have been approved and stay as the standard of care in their areas of action. Furthermore, a considerable number of peptibodies are currently in preclinical and clinical development.pt_PT
dc.description.sponsorshipPortuguese Funding Agency, Fundação para a Ciência e a Tecnologia, FCT IP, Grants Numbers: PD/BD/128281/2017, SFRH/ BPD/94466/2013, and PTDC/BBB-NAN/ 1578/2014; Marie Skłodowska-Curie Research and Innovation Staff Exchange (MSCA-RISE), call 20-MSCA-RISE-2014, Grant number: H20 644167–INPACT.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationPeptide Science. 2018;110:e23095pt_PT
dc.identifier.doi10.1002/bip.23095pt_PT
dc.identifier.issn2475-8817
dc.identifier.urihttp://hdl.handle.net/10451/37663
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWiley-PeptideSciencept_PT
dc.relationSFRH/ BPD/94466/2013pt_PT
dc.relationTrans-BBB peptides for targeting brain metastasis
dc.relationH20 644167–INPACT.pt_PT
dc.relation.publisherversionhttps://onlinelibrary.wiley.com/journal/24758817pt_PT
dc.subjectCopper-free click chemistrypt_PT
dc.subjectPeptibodypt_PT
dc.subjectPeptide-Fc fusion proteinpt_PT
dc.subjectSortase-mediated protein ligationpt_PT
dc.subjectStreamlined-expressed protein ligationpt_PT
dc.titlePeptibodies : an elegant solution for a long-standing problempt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleTrans-BBB peptides for targeting brain metastasis
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F128281%2F2017/PT
oaire.citation.startPagee23095.pt_PT
oaire.citation.titlePeptide Sciencept_PT
oaire.citation.volume110pt_PT
person.familyNameCavaco
person.familyNameCastanho
person.familyNameNeves
person.givenNameMarco
person.givenNameMiguel
person.givenNameVera
person.identifier1069324
person.identifier953259
person.identifier.ciencia-id1412-63B8-7494
person.identifier.ciencia-id671C-1860-A160
person.identifier.orcid0000-0002-0938-9038
person.identifier.orcid0000-0001-7891-7562
person.identifier.orcid0000-0002-2989-7208
person.identifier.ridO-2176-2018
person.identifier.scopus-author-id56605575600
person.identifier.scopus-author-id26537945300
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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relation.isAuthorOfPublicationf5e46f85-fabf-450a-9ee2-1c7b59410892
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relation.isAuthorOfPublication.latestForDiscoveryf62bb731-3f4d-4eaf-bc6b-dd379f6c2327
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