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Activation and allosteric modulation of a muscarinic acetylcholine receptor
TLDR
The structure of an agonist-bound, active state of the human M2 muscarinic acetylcholine receptor stabilized by a G-protein mimetic camelid antibody fragment isolated by conformational selection using yeast surface display reveals larger conformational changes in the extracellular region and orthosteric binding site than observed in the active states of the β2AR and rhodopsin. Expand
Structure-based discovery of opioid analgesics with reduced side effects
TLDR
PZM21 is a potent Gi activator with exceptional selectivity for μOR and minimal β-arrestin-2 recruitment and is devoid of both respiratory depression and morphine-like reinforcing activity in mice at equi-analgesic doses. Expand
Visualization and ligand-induced modulation of dopamine receptor dimerization at the single molecule level
TLDR
Using TIRF microscopy at the single molecule level, transient formation of homodimers of dopamine receptors in the membrane of stably transfected CHO cells has been observed and the equilibrium between dimers and monomers was modulated by the binding of ligands. Expand
Recent advances in the search for D3- and D4-selective drugs: probes, models and candidates.
TLDR
The very recent publication of the X-ray crystal structure of D(3) should facilitate efficient discovery of unprecedented chemotypes and the development of D (3)-selective agonists, functionally selective ligands and the exploitation of homo- and heteromers remain challenging. Expand
Covalent agonists for studying G protein-coupled receptor activation
TLDR
It is demonstrated that the tool compounds presented herein display an efficient covalent binding mode and that the respective covalently binding ligand-receptor complexes activate G proteins comparable to the natural neurotransmitters. Expand
In vitro affinities of various halogenated benzamide derivatives as potential radioligands for non-invasive quantification of D(2)-like dopamine receptors.
TLDR
Good properties are expected for the two iodinated compounds NAE and NADE regarding in vivo imaging with SPECT regarding in vitro affinities to dopaminergic, serotonergic and adrenergic receptors. Expand
Syntheses, Receptor Bindings, in vitro and in vivo Stabilities and Biodistributions of DOTA‐Neurotensin(8–13) Derivatives Containing β‐Amino Acid Residues – A Lesson about the Importance of Animal
TLDR
The amount of specifically bound radioligand is rather low and is confirmed by PET‐imaging experiments with the tumor‐bearing mice and by comparison of the in vitro plasma stability with the ex vivo blood content of the two 68Ga complexes shows that they are rapidly cleaved in the animals. Expand
Conformational Complexity and Dynamics in a Muscarinic Receptor Revealed by NMR Spectroscopy.
TLDR
It is shown that the M2R has a complex energy landscape in which ligands with different efficacy profiles stabilize distinct receptor conformations, allowing us to correlate ligand structure with changes in receptor structure and dynamics. Expand
An allosteric modulator binds to a conformational hub in the β2 adrenergic receptor
TLDR
A newly developed allosteric modulator of the β2-adrenergic receptor (β2AR), AS408, that binds to the membrane-facing surface of transmembrane segments 3 and 5, as revealed by X-ray crystallography. Expand
Interactive SAR studies: rational discovery of super-potent and highly selective dopamine D3 receptor antagonists and partial agonists.
TLDR
An interactive drug discovery process leading to heterocyclic bioisosteres is demonstrated and the benzothiophenes 3c and 3d revealed outstanding D3 affinity and subtype selectivity. Expand
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