Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid Stoffw Microb

Singer, NK; Sánchez-Murcia, PA; Ernst, M; González, L.
Unravelling the Turn-On Fluorescence Mechanism of a Fluorescein-Based Probe in GABA_A Receptors.
Angew Chem Int Ed Engl. 2022; 61(30):e202205198 Doi: 10.1002/anie.202205198 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz: Sánchez Murcia Pedro Alejandro
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Abstract:: GABA_A (γ-aminobutyric acid type A) receptors are ligand-gated ion channels mediating fast inhibitory transmission in the mammalian brain. Here we report the molecular and electronic mechanism governing the turn-on emission of a fluorescein-based imaging probe able to target the human GABA_A receptor. Multiscale calculations evidence a drastic conformational change of the probe from folded in solution to extended upon binding to the receptor. Intramolecular ππ-stacking interactions present in the folded probe are responsible for quenching fluorescence in solution. In contrast, unfolding within the GABA_A receptor changes the nature of the bright excited state triggering emission. Remarkably, this turn-on effect only manifests for the dianionic prototropic form of the imaging probe, which is found to be the strongest binder to the GABA_A receptor. This study is expected to assist the design of new photoactivatable screening tools for allosteric modulators of the GABA_A receptor.
Find related publications in this database (using NLM MeSH Indexing): Animals - administration & dosage; Fluorescein - administration & dosage; Fluorescence - administration & dosage; Humans - administration & dosage; Mammals - metabolism; Receptors, GABA-A - chemistry, metabolism; gamma-Aminobutyric Acid - pharmacology
Find related publications in this database (Keywords): Charge Transfer States; Fluorescent Probe; GABA-a Receptor; Gabazine; QM; MM