Discovery of kynurenines containing oligopeptides as potent opioid receptor agonists

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dc.contributor.authorSzucs, Edina
dc.contributor.authorStefanucci, Azzurra
dc.contributor.authorDimmito, Marilisa Pia
dc.contributor.authorZádor, Ferenc
dc.contributor.authorPieretti, Stefano
dc.contributor.authorZengin, Gökhan
dc.contributor.authorVécsei, László
dc.date.accessioned2020-03-26T20:20:46Z
dc.date.available2020-03-26T20:20:46Z
dc.date.issued2020
dc.departmentSelçuk Üniversitesi, Fen Fakültesi, Biyoloji Bölümüen_US
dc.description.abstractKynurenine (kyn) and kynurenic acid (kyna) are well-defined metabolites of tryptophan catabolism collectively known as “kynurenines”, which exert regulatory functions in host-microbiome signaling, immune cell response, and neuronal excitability. Kynurenine containing peptides endowed with opioid receptor activity have been isolated from natural organisms; thus, in this work, novel opioid peptide analogs incorporating L-kynurenine (L-kyn) and kynurenic acid (kyna) in place of native amino acids have been designed and synthesized with the aim to investigate the biological effect of these modifications. The kyna-containing peptide (KA1) binds selectively the ?-opioid receptor with a Ki = 1.08 ± 0.26 (selectivity ratio ?/?/? = 1:514:10000), while the L-kyn-containing peptide (K6) shows a mixed binding affinity for ?, ?, and ?-opioid receptors, with efficacy and potency (Emax = 209.7 + 3.4%; LogEC50 = ?5.984 + 0.054) higher than those of the reference compound DAMGO. This novel oligopeptide exhibits a strong antinociceptive effect after i.c.v. and s.c. administrations in in vivo tests, according to good stability in human plasma (t1/2 = 47 min). © 2020 by the authors. Licensee MDPI, Basel, Switzerland.en_US
dc.description.sponsorship20391?3/2018/FEKUSTRAT Nemzeti Kutatási Fejlesztési és Innovációs Hivatalen_US
dc.description.sponsorshipFunding: This research was supported by the project GINOP 2.3.2?15?2016?00034, provided by National Research, Development and Innovation Office (NKFI), Budapest, Hungary, and the Ministry of Human Capacities, Hungary grant 20391?3/2018/FEKUSTRAT.en_US
dc.identifier.citationSzucs, E., Stefanucci, A., Dimmito, M. P., Zádor, F., Pieretti, S., Zengin, G., Vécsei, L. (2020). Discovery Of Kynurenines Containing Oligopeptides As Potent Opioid Receptor Agonists. Biomolecules, 10,(2).
dc.identifier.doi10.3390/biom10020284en_US
dc.identifier.issn2218273Xen_US
dc.identifier.issue2en_US
dc.identifier.pmid32059524en_US
dc.identifier.scopusqualityN/Aen_US
dc.identifier.urihttps://dx.doi.org/10.3390/biom10020284
dc.identifier.urihttps://hdl.handle.net/20.500.12395/38665
dc.identifier.volume10en_US
dc.identifier.wosWOS:000522138500038en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorZengin, Gökhan
dc.language.isoenen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofBiomoleculesen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.selcuk20240510_oaigen_US
dc.subjectBinding affinityen_US
dc.subjectG-protein activationen_US
dc.subjectKynureninesen_US
dc.subjectPeptidesen_US
dc.subjectPharmacophoreen_US
dc.subject?-opioid receptoren_US
dc.titleDiscovery of kynurenines containing oligopeptides as potent opioid receptor agonistsen_US
dc.typeArticleen_US

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