Artykuł w czasopiśmie
Brak miniatury
Licencja
CC-BYCC-BY - Uznanie autorstwa
 

Multifunctional Enkephalin Analogs with a New Biological Profile: MOR/DOR Agonism and KOR Antagonism

Uproszczony widok
cris.lastimport.scopus2024-02-12T19:36:16Z
dc.abstract.enIn our previous studies, we developed a series of mixed MOR/DOR agonists that are enkephalin-like tetrapeptide analogs with an N-phenyl-N-piperidin-4-ylpropionamide (Ppp) moiety at the C-terminus. Further SAR study on the analogs, initiated by the findings from off-target screening, resulted in the discovery of LYS744 (6, Dmt-DNle-Gly-Phe(p-Cl)-Ppp), a multifunctional ligand with MOR/DOR agonist and KOR antagonist activity (GTPS assay: IC50 = 52 nM, Imax = 122% cf. IC50 = 59 nM, Imax = 100% for naloxone) with nanomolar range of binding affinity (Ki = 1.3 nM cf.Ki = 2.4 nM for salvinorin A). Based on its unique biological profile, 6 is considered to possess high therapeutic potential for the treatment of chronic pain by modulating pathological KOR activation while retaining analgesic efficacy attributed to its MOR/DOR agonist activity.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorMisicka-Kęsik, Aleksandra
dc.contributor.authorStreicher, John M.
dc.contributor.authorMolnar, Gabriella
dc.contributor.authorLaVigne, Justin
dc.contributor.authorPorreca, Frank
dc.contributor.authorWu, Zhijun
dc.contributor.authorTymecka, Dagmara
dc.contributor.authorRamos-Colon, Cyf
dc.contributor.authorRemesic, Michael
dc.contributor.authorLee, Yeon Sun
dc.contributor.authorHruby, Victor J.
dc.date.accessioned2024-01-25T13:06:07Z
dc.date.available2024-01-25T13:06:07Z
dc.date.copyright2021-05-31
dc.date.issued2021
dc.description.accesstimeAT_PUBLICATION
dc.description.financePublikacja bezkosztowa
dc.description.number6
dc.description.versionFINAL_PUBLISHED
dc.description.volume9
dc.identifier.doi10.3390/BIOMEDICINES9060625
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/113069
dc.identifier.weblinkhttps://www.mdpi.com/2227-9059/9/6/625/pdf
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofBiomedicines
dc.relation.pages625
dc.rightsCC-BY
dc.sciencecloudnosend
dc.subject.enAnalgesic effects
dc.subject.enKappa receptor antagonists
dc.subject.enMultifunctional activity
dc.subject.enOpioid receptors
dc.subject.enPeptidomimetics
dc.subject.enPlasma stability
dc.subject.enTemplate-based alignment modeling
dc.titleMultifunctional Enkephalin Analogs with a New Biological Profile: MOR/DOR Agonism and KOR Antagonism
dc.typeJournalArticle
dspace.entity.typePublication