Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/101384
Full metadata record
DC FieldValueLanguage
dc.contributor.authorLama, Dilrajen
dc.contributor.authorLakshminarayanan, Rajamanien
dc.contributor.authorLane, David P.en
dc.contributor.authorBrown, Christopher J.en
dc.contributor.authorQuah, Soo T.en
dc.contributor.authorVerma, Chandra S.en
dc.contributor.authorBeuerman, Roger W.en
dc.date.accessioned2014-01-21T05:30:54Zen
dc.date.accessioned2019-12-06T20:37:39Z-
dc.date.available2014-01-21T05:30:54Zen
dc.date.available2019-12-06T20:37:39Z-
dc.date.copyright2013en
dc.date.issued2013en
dc.identifier.citationLama, D., Quah, S. T., Verma, C. S., Lakshminarayanan, R., Beuerman, R. W., Lane, D. P., et al. (2013). Rational optimization of conformational effects induced by hydrocarbon staples in peptides and their binding interfaces. Scientific reports, 3, 1-10.en
dc.identifier.issn2045-2322en
dc.identifier.urihttps://hdl.handle.net/10356/101384-
dc.identifier.urihttp://hdl.handle.net/10220/18637en
dc.description.abstracteIF4E is frequently over-expressed in different cancers and causes increased translation of oncogenic proteins via deregulated cap-dependent translation. Inhibitors of the eIF4E:eIF4G interactions represent an approach that would normalize cap-dependent translation. Stapled peptides represent an emerging class of therapeutics that can target protein: protein interactions. We present here molecular dynamics simulations for a set of rationally designed stapled peptides in solution and in complex with eIF4E, supported with biophysical and crystallographic data. Clustering of the simulated structures revealed the favoured conformational states of the stapled peptides in their bound or free forms in solution. Identifying these populations has allowed us to design peptides with improved affinities by introducing mutations into the peptide sequence to alter their conformational distributions. These studies emphasise the effects that engineered mutations have on the conformations of free and bound peptides, and illustrate that both states must be considered in efforts to attain high affinity binding.en
dc.language.isoenen
dc.relation.ispartofseriesScientific reportsen
dc.rights© 2013 The Author(s). This paper was published in Scientific Reports and is made available as an electronic reprint (preprint) with permission of the Author(s). The paper can be found at the following official DOI: [http://dx.doi.org/10.1038/srep03451]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.en
dc.subjectDRNTU::Science::Biological sciencesen
dc.titleRational optimization of conformational effects induced by hydrocarbon staples in peptides and their binding interfacesen
dc.typeJournal Articleen
dc.contributor.schoolSchool of Biological Sciencesen
dc.identifier.doi10.1038/srep03451en
dc.description.versionPublished versionen
item.fulltextWith Fulltext-
item.grantfulltextopen-
Appears in Collections:SBS Journal Articles

Google ScholarTM

Check

Altmetric

Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.