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dc.contributor.authorMadden, Sarah K
dc.contributor.authorItzhaki, Laura S
dc.date.accessioned2022-01-28T14:46:48Z
dc.date.available2022-01-28T14:46:48Z
dc.date.issued2021-02-15
dc.identifier.citationProtein engineering, design & selection : PEDS, volume 34
dc.identifier.issn1741-0126
dc.identifier.other34882773
dc.identifier.otherPMC8660007
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/333107
dc.description.abstractThe process of displaying functional peptides by 'grafting' them onto loops of a stable protein scaffold can be used to impart binding affinity for a target, but it can be difficult to predict the affinity of the grafted peptide and the effect of grafting on scaffold stability. In this study, we show that a series of peptides that bind to the E3 ubiquitin ligase Keap1 can be grafted into the inter-repeat loop of a consensus-designed tetratricopeptide repeat (CTPR) protein resulting in proteins with high stability. We found that these CTPR-grafted peptides had similar affinities to their free peptide counterparts and achieved a low nanomolar range. This result is likely due to a good structural match between the inter-repeat loop of the CTPR and the Keap1-binding peptide. The grafting process led to the discovery of a new Keap1-binding peptide, Ac-LDPETGELL-NH2, with low nanomolar affinity for Keap1, highlighting the potential of the repeat-protein class for application in peptide display.
dc.description.sponsorshipCRUK Pioneer Award (C17838/A22676) CRUK Biotherapeutic Drug Discovery Project Award (C17838/A27225). BBSRC Doctoral Training Scholarship (BB/J014540/1
dc.languageeng
dc.publisherOxford University Press (OUP)
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 101186484
dc.sourceessn: 1741-0134
dc.subjectNRF2
dc.subjectBiologics
dc.subjectTetratricopeptide Repeat
dc.subjectPeptide Grafting
dc.subjectTandem-repeat Protein
dc.titleExploring the binding of rationally engineered tandem-repeat proteins to E3 ubiquitin ligase Keap1.
dc.typeArticle
dc.date.updated2022-01-28T14:46:47Z
prism.publicationNameProtein Eng Des Sel
dc.identifier.doi10.17863/CAM.80531
dcterms.dateAccepted2021-10-04
rioxxterms.versionofrecord10.1093/protein/gzab027
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidItzhaki, Laura S [0000-0001-6504-2576]
dc.identifier.eissn1741-0134
pubs.funder-project-idCancer Research UK (22676)
pubs.funder-project-idCancer Research UK (27225)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/J014540/1)
cam.issuedOnline2021-12-09


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International