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A Focus on Unusual ECL2 Interactions Yields β 2 ‐Adrenergic Receptor Antagonists with Unprecedented Scaffolds
Author(s) -
Scharf Magdalena M.,
Zimmermann Mirjam,
Wilhelm Florian,
Stroe Raimond,
Waldhoer Maria,
Kolb Peter
Publication year - 2020
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201900715
Subject(s) - focus (optics) , adrenergic receptor , chemistry , adrenergic , β2 adrenergic receptor , combinatorial chemistry , pharmacology , receptor , stereochemistry , biochemistry , medicine , physics , agonist , optics
Abstract 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 β 2 ‐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.