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dc.contributor.authorSerrano, JCen
dc.contributor.authorSipthorp, Jen
dc.contributor.authorXu, Wenshuen
dc.contributor.authorItzhaki, Lauraen
dc.contributor.authorLey, Stevenen
dc.date.accessioned2017-04-12T09:51:53Z
dc.date.available2017-04-12T09:51:53Z
dc.date.issued2017-05-18en
dc.identifier.issn1439-4227
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/263622
dc.description.abstractStapled peptides have arisen as a new class of chemical probe and potential therapeutic agents to modulate protein-protein interactions. Here, we report the first two-component i,i+7 stapling methodology using two orthogonal, on-resin stapling reactions to incorporate linkers bearing a chiral center on a p53-derived stapled peptide. Post-stapling modifications to the staple chain were performed on-resin, enabling rapid access to various peptide derivatives from a single staple. The stapled peptides have increased helicity, protease stability and in vitro binding affinities to MDM2 compared to the unstapled peptide. This approach can be used to generate a diverse library of stapled peptides with differing properties starting from a single stapled peptide, with scope for much greater functional diversity than that provided by existing stapling methodologies.
dc.description.sponsorshipThis work was supported by Engineering and Physical Sciences Research Council (EPSRC) grants EP/K009494/1, EP/M004120/1 and EP/K/039520/1. JCS acknowledges a scholarship from the Gates Cambridge Trust. LSI acknowledges the support of a Senior Fellowship from the Medical Research Foundation.
dc.language.isoenen
dc.publisherJohn Wiley & Sons Ltd.
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectchiral linkersen
dc.subjectprotein–protein interactionsen
dc.subjectsolid-phase synthesisen
dc.subjectstapled peptidesen
dc.subjecttwo-component staplingen
dc.titleA Novel Methodology for the Incorporation of Chiral Linkers in Stapled Peptidesen
dc.typeArticle
prism.endingPage1071
prism.issueIdentifier12en
prism.publicationDate2017en
prism.publicationNameChembiochem : a European journal of chemical biologyen
prism.startingPage1066
prism.volume18en
dc.identifier.doi10.17863/CAM.8979
dcterms.dateAccepted2017-04-07en
rioxxterms.versionofrecord10.1002/cbic.201700075en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2017-05-18en
dc.contributor.orcidItzhaki, Laura [0000-0001-6504-2576]
dc.contributor.orcidLey, Steven [0000-0002-7816-0042]
dc.identifier.eissn1439-7633
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idEPSRC (EP/K009494/1)
pubs.funder-project-idEPSRC (EP/M004120/1)
pubs.funder-project-idMRC (G1002329)
pubs.funder-project-idMRC (MC_PC_14116 v2)
pubs.funder-project-idMRC (MC_PC_13059)
cam.issuedOnline2017-04-07en
dc.identifier.urlhttps://onlinelibrary.wiley.com/doi/full/10.1002/cbic.201700075en
rioxxterms.freetoread.startdate2018-04-07


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