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Thioether Analogues of Disulfide-Bridged Cyclic Peptides Targeting Death Receptor 5: Conformational Analysis, Dimerisation and Consequences for Receptor Activation

dc.contributor.authorPULKA-ZIACH, Karolina
dc.contributor.authorPAVET, Valeria
dc.contributor.authorCHEKKAT, Neila
dc.contributor.authorESTIEU-GIONNET, Karine
dc.contributor.authorROHAC, Roman
dc.contributor.authorLECHNER, Marie-Charlotte
dc.contributor.authorSMULSKI, Cristian R.
dc.contributor.authorZEDER-LUTZ, Gabrielle
dc.contributor.authorALTSCHUH, Daniele
dc.contributor.authorGRONEMEYER, Hinrich
dc.contributor.authorFOURNEL, Sylvie
dc.contributor.authorODAERT, Benoit
dc.contributor.authorGUICHARD, Gilles
IDREF: 084339268
dc.date.accessioned2020-09-03T08:01:56Z
dc.date.available2020-09-03T08:01:56Z
dc.date.issued2015
dc.identifier.issn1439-4227
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/10934
dc.description.abstractEnCyclic peptides containing redox-stable thioether bridges might provide a useful alternative to disulfide-bridged bioactive peptides. We report the effect of replacing the disulfide bridge with a lanthionine linkage in a 16-mer cyclic peptide that binds to death receptor 5 (DR5, TRAIL-R2). Upon covalent oligomerisation, the disulfide-bridged peptide has previously shown similar behaviour to that of TNF-related apoptosis inducing ligand (TRAIL), by selectively triggering the DR5 cell death pathway. The structural and biological properties of the DR5-binding peptide and its desulfurised analogue were compared. Surface plasmon resonance (SPR) data suggest that these peptides bind DR5 with comparable affinities. The same holds true for dimeric versions of these peptides: the thioether is able to induce DR5-mediated apoptosis of BJAB lymphoma and tumorigenic BJELR cells, albeit to a slightly lower extent compared to its disulfide homologue. NMR analysis revealed subtle variation in the conformations of the two peptides and suggests that the thioether peptide is slightly less folded than its disulfide homologue. These observations could account for the different capability of the two dimers to cluster DR5 receptors on the cell surface and to trigger apoptosis. Nevertheless, our results suggest that the thioether peptide is a potential candidate for evaluation in animal models.
dc.language.isoen
dc.title.enThioether Analogues of Disulfide-Bridged Cyclic Peptides Targeting Death Receptor 5: Conformational Analysis, Dimerisation and Consequences for Receptor Activation
dc.typeArticle de revue
dc.identifier.doi10.1002/cbic.201402485
dc.subject.halChimie/Matériaux
bordeaux.journalChembiochem
bordeaux.page293-301
bordeaux.volume16
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN) - UMR 5248*
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN, UMR 5248)
bordeaux.issue2
bordeaux.institutionUniversité de Bordeaux
bordeaux.institutionBordeaux INP
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Chembiochem&rft.date=2015&rft.volume=16&rft.issue=2&rft.spage=293-301&rft.epage=293-301&rft.eissn=1439-4227&rft.issn=1439-4227&rft.au=PULKA-ZIACH,%20Karolina&PAVET,%20Valeria&CHEKKAT,%20Neila&ESTIEU-GIONNET,%20Karine&ROHAC,%20Roman&rft.genre=article


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