Identification of the Beer Component Hordenine as Food-Derived Dopamine D2 Receptor Agonist by Virtual Screening a 3D Compound Database.

Beitrag in einer Fachzeitschrift
(Originalarbeit)


Details zur Publikation

Autor(en): Sommer T, Hübner H, El Kerdawy A, Gmeiner P, Pischetsrieder M, Clark T
Zeitschrift: Scientific Reports
Jahr der Veröffentlichung: 2017
Band: 7
Seitenbereich: 44201
ISSN: 2045-2322


Abstract


The dopamine D2 receptor (D2R) is involved in food reward and compulsive food intake. The present study developed a virtual screening (VS) method to identify food components, which may modulate D2R signalling. In contrast to their common applications in drug discovery, VS methods are rarely applied for the discovery of bioactive food compounds. Here, databases were created that exclusively contain substances occurring in food and natural sources (about 13,000 different compounds in total) as the basis for combined pharmacophore searching, hit-list clustering and molecular docking into D2R homology models. From 17 compounds finally tested in radioligand assays to determine their binding affinities, seven were classified as hits (hit rate = 41%). Functional properties of the five most active compounds were further examined in β-arrestin recruitment and cAMP inhibition experiments. D2R-promoted G-protein activation was observed for hordenine, a constituent of barley and beer, with approximately identical ligand efficacy as dopamine (76%) and a Ki value of 13 μM. Moreover, hordenine antagonised D2-mediated β-arrestin recruitment indicating functional selectivity. Application of our databases provides new perspectives for the discovery of bioactive food constituents using VS methods. Based on its presence in beer, we suggest that hordenine significantly contributes to mood-elevating effects of beer.



FAU-Autoren / FAU-Herausgeber

Clark, Timothy apl. Prof. Dr.
Computer-Chemie-Centrum
Gmeiner, Peter Prof. Dr.
Lehrstuhl für Pharmazeutische Chemie
Hübner, Harald Dr.
Lehrstuhl für Pharmazeutische Chemie
Pischetsrieder, Monika Prof. Dr.
Lehrstuhl für Lebensmittelchemie (Henriette-Schmidt-Burkhardt Lehrstuhl)
Sommer, Thomas
Lehrstuhl für Lebensmittelchemie (Henriette-Schmidt-Burkhardt Lehrstuhl)


Zusätzliche Organisationseinheit(en)
Emil-Fischer-Zentrum (Emil Fischer Center)


Autor(en) der externen Einrichtung(en)
Cairo University


Zitierweisen

APA:
Sommer, T., Hübner, H., El Kerdawy, A., Gmeiner, P., Pischetsrieder, M., & Clark, T. (2017). Identification of the Beer Component Hordenine as Food-Derived Dopamine D2 Receptor Agonist by Virtual Screening a 3D Compound Database. Scientific Reports, 7, 44201. https://dx.doi.org/10.1038/srep44201

MLA:
Sommer, Thomas, et al. "Identification of the Beer Component Hordenine as Food-Derived Dopamine D2 Receptor Agonist by Virtual Screening a 3D Compound Database." Scientific Reports 7 (2017): 44201.

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Zuletzt aktualisiert 2018-18-10 um 02:10