Differently fluorescence-labelled dibenzodiazepinone-type muscarinic acetylcholine receptor ligands with high M2R affinity

Corinna G. Gruber; Andrea Pegoli; Christoph Müller; Lukas Grätz; Xueke She; Max Keller

doi:10.1039/D0MD00137F

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Differently fluorescence-labelled dibenzodiazepinone-type muscarinic acetylcholine receptor ligands with high M₂R affinity†

Corinna G. Gruber,

^a Andrea Pegoli,^a Christoph Müller,

^a Lukas Grätz,

^a Xueke She^a and Max Keller

*^a

Author affiliations

* Corresponding authors

^a Institute of Pharmacy, Faculty of Chemistry and Pharmacy, University of Regensburg, Universitätsstrasse 31, D-93053 Regensburg, Germany
E-mail: max.keller@ur.de

Abstract

A series of fluorescent dibenzodiazepinone-type muscarinic acetylcholine M₂ receptor (M₂R) ligands was synthesized using various fluorescent dyes (5-TAMRA, λ_ex/λ_em ≈ 547/576 nm; BODIPY 630/650, λ_ex/λ_em ≈ 625/640 nm; pyridinium dye Py-1, λ_ex/λ_em ≈ 611/665 nm and pyridinium dye Py-5, λ_ex/λ_em ≈ 465/732 nm). All fluorescent probes exhibited high M₂R affinity (pK_i (radioligand competition binding): 8.75-9.62, pK_d (flow cytometry): 8.36–9.19), a very low preference for the M₂R over the M₁ and M₄ receptors and moderate to pronounced M₂R selectivity compared to the M₃ and M₅ receptors. The presented fluorescent ligands are considered useful molecular tools for future studies using methods such as fluorescence anisotropy and BRET based MR binding assays.

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Article information

DOI: https://doi.org/10.1039/D0MD00137F
Article type: Research Article
Submitted: 24 Apr 2020
Accepted: 20 May 2020
First published: 08 Jun 2020

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RSC Med. Chem., 2020,11, 823-832

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Differently fluorescence-labelled dibenzodiazepinone-type muscarinic acetylcholine receptor ligands with high M₂R affinity

C. G. Gruber, A. Pegoli, C. Müller, L. Grätz, X. She and M. Keller, RSC Med. Chem., 2020, 11, 823 DOI: 10.1039/D0MD00137F

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