dc.contributor.author | Jung, Kwan-Young | |
dc.contributor.author | Wang, Huabo | |
dc.contributor.author | Teriete, Peter | |
dc.contributor.author | Yap, Jeremy L | |
dc.contributor.author | Chen, Lijia | |
dc.contributor.author | Lanning, Maryanna E | |
dc.contributor.author | Hu, Angela | |
dc.contributor.author | Lambert, Lester J | |
dc.contributor.author | Holien, Toril | |
dc.contributor.author | Sundan, Anders | |
dc.contributor.author | Cosford, Nicholas D P | |
dc.contributor.author | Prochownik, Edward V | |
dc.contributor.author | Fletcher, Steven | |
dc.date.accessioned | 2017-12-12T09:23:51Z | |
dc.date.available | 2017-12-12T09:23:51Z | |
dc.date.created | 2015-07-13T12:55:50Z | |
dc.date.issued | 2015 | |
dc.identifier.citation | Journal of Medicinal Chemistry. 2015, 58 (7), 3002-3024. | nb_NO |
dc.identifier.issn | 0022-2623 | |
dc.identifier.uri | http://hdl.handle.net/11250/2470572 | |
dc.description.abstract | The rational design of inhibitors of the bHLH-ZIP oncoprotein c-Myc is hampered by a lack of structure in its monomeric state. We describe herein the design of novel, low-molecular-weight, synthetic α-helix mimetics that recognize helical c-Myc in its transcriptionally active coiled-coil structure in association with its obligate bHLH-ZIP partner Max. These compounds perturb the heterodimer’s binding to its canonical E-box DNA sequence without causing protein–protein dissociation, heralding a new mechanistic class of “direct” c-Myc inhibitors. In addition to electrophoretic mobility shift assays, this model was corroborated by further biophysical methods, including NMR spectroscopy and surface plasmon resonance. Several compounds demonstrated a 2-fold or greater selectivity for c-Myc–Max heterodimers over Max–Max homodimers with IC50 values as low as 5.6 μM. Finally, these compounds inhibited the proliferation of c-Myc-expressing cell lines in a concentration-dependent manner that correlated with the loss of expression of a c-Myc-dependent reporter plasmid despite the fact that c-Myc–Max heterodimers remained intact. | nb_NO |
dc.language.iso | eng | nb_NO |
dc.publisher | American Chemical Society | nb_NO |
dc.title | Perturbation of the c-Myc-Max Protein-Protein Interaction via Synthetic α-Helix Mimetics | nb_NO |
dc.type | Journal article | nb_NO |
dc.type | Peer reviewed | nb_NO |
dc.description.version | acceptedVersion | nb_NO |
dc.source.pagenumber | 3002-3024 | nb_NO |
dc.source.volume | 58 | nb_NO |
dc.source.journal | Journal of Medicinal Chemistry | nb_NO |
dc.source.issue | 7 | nb_NO |
dc.identifier.doi | 10.1021/jm501440q | |
dc.identifier.cristin | 1253664 | |
dc.relation.project | Stiftelsen Kristian Gerhard Jebsen: SKGJ-MED-007 | nb_NO |
dc.relation.project | Norges forskningsråd: 223255 | nb_NO |
dc.relation.project | Kreftforeningen: 2215992 | nb_NO |
dc.description.localcode | © 2015 American Chemical Society.This document is the Accepted Manuscript version of a Published Work that appeared in final form after peer review and technical editing by the publisher. To access the final edited and published work see dx.doi.org/10.1021/jm501440q | nb_NO |
cristin.unitcode | 194,65,15,0 | |
cristin.unitname | Institutt for klinisk og molekylær medisin | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |