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dc.contributor.authorRosier, Niklas
dc.contributor.authorMönnich, Denise
dc.contributor.authorNagl, Martin
dc.contributor.authorSchihada, Hannes
dc.contributor.authorSirbu, Alexei
dc.contributor.authorKonar, Nergis
dc.contributor.authorReyes-Resina, Irene
dc.contributor.authorNavarro, Gemma
dc.contributor.authorFranco, Rafael
dc.contributor.authorKolb, Peter
dc.contributor.authorAnnibale, Paolo
dc.contributor.authorPockes, Steffen
dc.identifier.citationRosier , N , Mönnich , D , Nagl , M , Schihada , H , Sirbu , A , Konar , N , Reyes-Resina , I , Navarro , G , Franco , R , Kolb , P , Annibale , P & Pockes , S 2023 , ' Shedding light on the D 1 -like receptors : a fluorescence-based toolbox for visualization of the D 1 and D 5 receptors ' , ChemBioChem , vol. Early View , e202300658 .
dc.identifier.otherRIS: urn:B66DADAD47F524D39680B63A3576110E
dc.identifier.otherORCID: /0000-0003-3208-5347/work/147967176
dc.descriptionFunding: Universitat de Barcelona; Fonds der Chemischen Industrie. Grant Number: 661688; University of Regensburg graduate school “Receptor Dynamics: Emerging Paradigms for Novel Drugs. Grant Number: K-BM-2013-247; Elite Network of Bavaria Deutsche Forschungsgemeinschaft. Grant Numbers: 421152132, SFB1423, SFB1470; Spanish MCIN/AEI/10.13039/501100011033. Grant Number: PID2021-126600OB−I00; European Union Next Generation EU/PRTR.en
dc.description.abstractDopamine D1-like receptors are the most abundant type of dopamine receptors in the central nervous system and, even after decades of discovery, still highly interesting for the study of neurological diseases. We herein describe the synthesis of a new set of fluorescent ligands, structurally derived from D1R antagonist SCH-23390 and labeled with two different fluorescent dyes, as tool compounds for the visualization of D1-like receptors. Pharmacological characterization in radioligand binding studies identified UR-NR435 (25) as a high-affinity ligand for D1-like receptors (pKi (D1R) = 8.34, pKi (D5R) = 7.62) with excellent selectivity towards D2-like receptors. Compound 25 proved to be a neutral antagonist at the D1R and D5R in a Gs heterotrimer dissociation assay, an important feature to avoid receptor internalization and degradation when working with whole cells. The neutral antagonist 25 displayed rapid association and complete dissociation to the D1R in kinetic binding studies using confocal microscopy verifying its applicability for fluorescence microscopy. Moreover, molecular brightness studies determined a single-digit nanomolar binding affinity of the ligand, which was in good agreement with radioligand binding data. For this reason, this fluorescent ligand is a useful tool for a sophisticated characterization of native D1 receptors in a variety of experimental setups.
dc.subjectConfocal microscopyen
dc.subjectD1-like receptorsen
dc.subjectDopamine receptorsen
dc.subjectFluorescent ligandsen
dc.subjectMolecular brightnessen
dc.subjectQC Physicsen
dc.titleShedding light on the D1-like receptors : a fluorescence-based toolbox for visualization of the D1 and D5 receptorsen
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews. School of Physics and Astronomyen
dc.description.statusPeer revieweden

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