Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Singer, NK; Sánchez-Murcia, PA; Ernst, M; González, L.
Unravelling the Turn-On Fluorescence Mechanism of a Fluorescein-Based Probe in GABAA Receptors.
Angew Chem Int Ed Engl. 2022; 61(30):e202205198
Doi: 10.1002/anie.202205198
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- Leading authors Med Uni Graz
- Sánchez Murcia Pedro Alejandro
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- Abstract:
- GABAA (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 GABAA 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 GABAA 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 GABAA receptor. This study is expected to assist the design of new photoactivatable screening tools for allosteric modulators of the GABAA 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