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Ureidopeptide GLP-1 analogues with prolonged activity in vivo via signal bias and altered receptor trafficking

dc.rights.licenseopenen_US
dc.relation.isnodouble1831b7d8-b9d9-4cd5-bf38-f49e2736a213*
dc.contributor.authorFREMAUX, J.
dc.contributor.authorVENIN, C.
dc.contributor.authorMAURAN, L.
dc.contributor.authorZIMMER, R.
dc.contributor.authorKOENSGEN, F.
dc.contributor.authorROGNAN, D.
dc.contributor.authorBITSI, S.
dc.contributor.authorLUCEY, M. A.
dc.contributor.authorJONES, B.
dc.contributor.authorTOMAS, A.
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorGUICHARD, Gilles
dc.contributor.authorGOUDREAU, S. R.
dc.date.accessioned2020-05-19T14:17:16Z
dc.date.available2020-05-19T14:17:16Z
dc.date.issued2019
dc.identifier.issn2041-6520en_US
dc.identifier.otherhttp://www.rsc.org/suppdata/c9/sc/c9sc02079a/c9sc02079a1.pdfen_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/7639
dc.description.abstractEnThe high demand of the pharmaceutical industry for new modalities to address the diversification of biological targets with large surfaces of interaction led us to investigate the replacement of alpha-amino acid residues with ureido units at selected positions in peptides to improve potency and generate effective incretin mimics. Based on molecular dynamics simulations, N-terminally modified GLP-1 analogues with a ureido residue replacement at position 2 were synthesized and showed preservation of agonist activity while exhibiting a substantial increase in stability. This enabling platform was applied to exenatide and lixisenatide analogues to generate two new ureidopeptides with antidiabetic properties and longer duration of action. Further analyses demonstrated that the improvement was due mainly to differences in signal bias and trafficking of the GLP-1 receptor. This study demonstrates the efficacy of single alpha-amino acid substitution with ureido residues to design long lasting peptides.
dc.description.sponsorshipSynthèse et application en catalyse de complexes cyclométalés du fer obtenus par activation C-H - ANR-15-CE07-0001en_US
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/us/*
dc.title.enUreidopeptide GLP-1 analogues with prolonged activity in vivo via signal bias and altered receptor trafficking
dc.typeArticle de revueen_US
dc.identifier.doi10.1039/c9sc02079a
dc.subject.halChimie/Matériauxen_US
bordeaux.journalChemical Scienceen_US
bordeaux.page9872-9879en_US
bordeaux.volume10en_US
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN) - UMR 5248en_US
bordeaux.issue42en_US
bordeaux.institutionBordeaux INPen_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03182232
hal.version1
hal.date.transferred2021-03-26T10:13:51Z
hal.exporttrue
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