A5070488056- Receptor Mechanisms and Signaling
- Photochromic and Fluorescence Chemistry
- Nicotinic Acetylcholine Receptors Study
- Marine Toxins and Detection Methods
- Sleep and Wakefulness Research
- Circadian rhythm and melatonin
- Neuropeptides and Animal Physiology
- Biochemical and Structural Characterization
- Photoreceptor and optogenetics research
- Oxidative Organic Chemistry Reactions
- bioluminescence and chemiluminescence research
- Medical Imaging Techniques and Applications
- Ion channel regulation and function
- Chemical Synthesis and Analysis
- Synthesis and Biological Evaluation
- Fluorine in Organic Chemistry
- Radical Photochemical Reactions
- Sleep and related disorders
- Neurotransmitter Receptor Influence on Behavior
- Monoclonal and Polyclonal Antibodies Research
- Lanthanide and Transition Metal Complexes
Friedrich-Alexander-Universität Erlangen-Nürnberg
2021-2025
The β2‐adrenergic receptor (β2AR) is a critical target for the treatment of airway diseases such as asthma or chronic obstructive pulmonary disease (COPD). To better understand its mechanism action and study dynamics, photoswitchable ligands provide distinct advantage due to their ability be activated with high spatiotemporal control. In this study, we developed series molecular tools featuring different combinations pharmacophores, covalent warheads, linker lengths. These compounds were...
The β2‐adrenergic receptor (β2AR) is a critical target for the treatment of airway diseases such as asthma or chronic obstructive pulmonary disease (COPD). To better understand its mechanism action and study dynamics, photoswitchable ligands provide distinct advantage due to their ability be activated with high spatiotemporal control. In this study, we developed series molecular tools featuring different combinations pharmacophores, covalent warheads, linker lengths. These compounds were...
Abstract Dinoflagellates and cyanobacteria produce saxitoxin (STX) ~50 congeners that disrupt bioelectrical signals by blocking voltage-gated sodium channels (Na V s). Consuming seafood carrying these toxins causes paralytic shellfish poisoning (PSP). Although Na s anuran STX binding proteins (saxiphilins, Sxphs) use convergent modes, the structural basis for congener recognition is unknown. Here, we show American bullfrog ( Rana catesbeiana ) Rc Sxph High Himalaya frog Nanorana parkeri Np...
Molecular imaging using positron emission tomography (PET) can serve as a promising tool for visualizing biological targets in the brain. Insights into expression pattern and vivo of G protein-coupled orexin receptors OX1R OX2R will further our understanding system its role various physiological pathophysiological processes. Guided by crystal structures lead compound JH112 approved hypnotic drug suvorexant bound to OX2R, respectively, we herein describe design synthesis two novel...
Molecular imaging using positron emission tomography (PET) can serve as a promising tool for visualizing biological targets in the brain. Insights into expression pattern and vivo of G protein-coupled orexin receptors OX1R OX2R will further our understanding system its role various physiological pathophysiological processes. Guided by crystal structures lead compound JH112 approved hypnotic drug suvorexant bound to OX2R, respectively, we herein describe design synthesis two novel...
The family of neuropeptide Y (NPY) receptors comprises four subtypes (Y1R, Y2R, Y4R, Y5R), which are addressed by at least three endogenous peptides, i.e., NPY, peptide YY, and pancreatic polypeptide (PP), the latter showing a preference for Y4R. A series cyclic oligopeptidic Y4R ligands were prepared applying novel approach, N-terminus to arginine side-chain cyclization. Most peptides acted as partial agonists, up 60-fold higher affinity compared linear precursor peptides. Two hexapeptides...
Background: The orexin receptor (OXR) plays a role in drug addiction and appears as tumor marker colon carcinoma. Subtype-selective OXR PET ligands have not yet been reported. present work deals with the development of 18F-labeled dervived from selective OX1R antagonist JH112. Methods: Applying computational analysis, medicinal chemistry, integrated binding studies, Cu-mediated 18F-fluorination initial small animal we evaluated series (1a-1f), varying heteroarene scaffold FH112 by...
Abstract The G protein-coupled serotonin receptor 5-HT 1A R mediates antinociception and may serve as a valuable target for the treatment of pain. Starting from chemical library, ST171, bitopic chemotype activating was evolved. In vitro pharmacological investigations ST171 revealed potent selective i activation (EC 50 = 0.3 nM), with marginal s β-arrestin recruitment. Preclinical studies in mice showed that effective acute chronic (inflammatory neuropathic) pain models, without causing...
Dinoflagellates and cyanobacteria in harmful 'red tide' algal blooms produce saxitoxin (STX) ~50 congeners that block voltage gated sodium channel (NaV) function disrupt bioelectrical signals1-4. Consuming seafood carrying these lethal toxins causes paralytic shellfish poisoning (PSP), a growing public health hazard due to climate change5-7 motivates efforts detect counteract their noxious effects. Although structural studies of NaVs8,9 anuran soluble STX binding proteins known as...
Abstract Background The orexin receptor (OXR) plays a role in drug addiction and is aberrantly expressed colorectal tumors. Subtype-selective OXR PET ligands suitable for vivo use have not yet been reported. This work reports the development of 18 F-labeled ligand candidates derived from antagonist suvorexant OX1R-selective JH112. Results Computational analysis predicted that fluorine substitution (1e) introduction fluorobenzothiazole scaffold (1f) would be maintaining high OX1R affinity....