A Focus on Unusual ECL2 Interactions Yields β2 -Adrenergic Receptor Antagonists with Unprecedented Scaffolds.
Magdalena M ScharfMirjam ZimmermannFlorian WilhelmRaimond StroeMaria WaldhoerPeter KolbPublished in: ChemMedChem (2020)
The binding pockets of aminergic G protein-coupled receptors are often targeted by drugs and virtual screening campaigns. In order to find ligands with unprecedented scaffolds for one of the best-investigated receptors of this subfamily, the β2 -adrenergic receptor, we conducted a docking-based screen insisting that molecules would address previously untargeted residues in extracellular loop 2. We here report the discovery of ligands with a previously undescribed coumaran-based scaffold. Furthermore, we provide an analysis of the added value that X-ray structures in different conformations deliver for such docking screens.
Keyphrases
- tissue engineering
- high throughput
- molecular dynamics
- protein protein
- molecular dynamics simulations
- small molecule
- high resolution
- mass spectrometry
- genome wide
- binding protein
- cancer therapy
- transcription factor
- atomic force microscopy
- liquid chromatography
- dual energy
- high resolution mass spectrometry
- gas chromatography mass spectrometry
- magnetic resonance imaging
- drug delivery
- high speed