Novel Xanomeline-Containing Bitopic Ligands of Muscarinic Acetylcholine Receptors: Design, Synthesis and FRET Investigation.

ABSTRACT: In the last few years, fluorescence resonance energy transfer (FRET) receptor sensors have contributed to the understanding of GPCR ligand binding and functional activation. FRET sensors based on muscarinic acetylcholine receptors (mAChRs) have been employed to study dual-steric ligands, allowing for the detection of different kinetics and distinguishing between partial, full, and super agonism. Herein, we report the synthesis of the two series of bitopic ligands, 12-Cn and 13-Cn, and their pharmacological investigation at the M₁, M₂, M₄, and M₅ FRET-based receptor sensors. The hybrids were prepared by merging the pharmacophoric moieties of the M₁/M₄-preferring orthosteric agonist Xanomeline 10 and the M

SUBMITTER: Matera C 

PROVIDER: S-EPMC10005175 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature