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dc.contributor.authorIegre, Jessica
dc.contributor.authorBrear, Paul
dc.contributor.authorBaker, David J
dc.contributor.authorTan, Yaw Sing
dc.contributor.authorAtkinson, Eleanor L
dc.contributor.authorSore, Hannah F
dc.contributor.authorO' Donovan, Daniel H
dc.contributor.authorVerma, Chandra S
dc.contributor.authorHyvönen, Marko
dc.contributor.authorSpring, David R
dc.date.accessioned2019-04-26T23:30:22Z
dc.date.available2019-04-26T23:30:22Z
dc.date.issued2019-05-21
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-eCollection
dc.languageeng
dc.publisherRoyal Society of Chemistry (RSC)
dc.rightsAll rights reserved
dc.titleEfficient development of stable and highly functionalised peptides targeting the CK2α/CK2β protein-protein interaction.
dc.typeArticle
prism.endingPage5063
prism.issueIdentifier19
prism.publicationDate2019
prism.publicationNameChem Sci
prism.startingPage5056
prism.volume10
dc.identifier.doi10.17863/CAM.39187
dcterms.dateAccepted2019-04-11
rioxxterms.versionofrecord10.1039/c9sc00798a
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2019-05
dc.contributor.orcidIegre, Jessica [0000-0002-9074-653X]
dc.contributor.orcidBrear, Paul [0000-0002-4045-0474]
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 R [0000-0001-7355-2824]
dc.identifier.eissn2041-6539
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (107714/Z/15/Z)
pubs.funder-project-idEngineering and Physical Sciences Research Council (EP/P020291/1)
pubs.funder-project-idWellcome Trust (090340/Z/09/Z)
cam.issuedOnline2019-04-12
rioxxterms.freetoread.startdate2020-12-25


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