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dc.contributor.authorIegre, Jessicaen
dc.contributor.authorBrear, Paulen
dc.contributor.authorBaker, David Jen
dc.contributor.authorTan, Yaw Singen
dc.contributor.authorAtkinson, Eleanor Len
dc.contributor.authorSore, Hannahen
dc.contributor.authorO' Donovan, Daniel Hen
dc.contributor.authorVerma, Chandra Sen
dc.contributor.authorHyvönen, Markoen
dc.contributor.authorSpring, Daviden
dc.date.accessioned2019-04-26T23:30:22Z
dc.date.available2019-04-26T23:30:22Z
dc.date.issued2019-05en
dc.identifier.issn2041-6520
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/292034
dc.description.abstractThe discovery of new Protein–Protein Interaction (PPI) modulators is currently limited by the difficulties associated with the design and synthesis of selective small molecule inhibitors. Peptides are a potential solution for disrupting PPIs; however, they typically suffer from poor stability in vivo and limited tissue penetration hampering their wide spread use as new chemical biology tools and potential therapeutics. In this work, a combination of CuAAC chemistry, molecular modelling, X-ray crystallography, and biological validation allowed us to develop highly functionalised peptide PPI inhibitors of the protein CK2. The lead peptide, CAM7117, prevents the formation of the holoenzyme assembly in vitro, slows down proliferation, induces apoptosis in cancer cells and is stable in human serum. CAM7117 could aid the development of novel CK2 inhibitors acting at the interface and help to fully understand the intracellular pathways involving CK2. Importantly, the approach adopted herein could be applied to many PPI targets and has the potential to ease the study of PPIs by efficiently providing access to functionalised peptides.
dc.format.mediumElectronic-eCollectionen
dc.languageengen
dc.publisherRoyal Society of Chemistry (RSC)
dc.rightsAll rights reserved
dc.rights.uri
dc.titleEfficient development of stable and highly functionalised peptides targeting the CK2α/CK2β protein-protein interaction.en
dc.typeArticle
prism.endingPage5063
prism.issueIdentifier19en
prism.publicationDate2019en
prism.publicationNameChemical scienceen
prism.startingPage5056
prism.volume10en
dc.identifier.doi10.17863/CAM.39187
dcterms.dateAccepted2019-04-11en
rioxxterms.versionofrecord10.1039/c9sc00798aen
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-05en
dc.contributor.orcidIegre, Jessica [0000-0002-9074-653X]
dc.contributor.orcidBrear, Paul [0000-0002-4045-0474]
dc.contributor.orcidTan, Yaw Sing [0000-0002-2522-9421]
dc.contributor.orcidSore, Hannah [0000-0002-6542-0394]
dc.contributor.orcidO' Donovan, Daniel H [0000-0002-8400-2198]
dc.contributor.orcidVerma, Chandra S [0000-0003-0733-9798]
dc.contributor.orcidHyvönen, Marko [0000-0001-8683-4070]
dc.contributor.orcidSpring, David [0000-0001-7355-2824]
dc.identifier.eissn2041-6539
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWELLCOME TRUST (107714/Z/15/Z)
pubs.funder-project-idEPSRC (EP/P020291/1)
pubs.funder-project-idWellcome Trust (090340/Z/09/Z)
rioxxterms.freetoread.startdate2020-12-25


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