540 Chemie und zugeordnete Wissenschaften
Refine
Year of publication
- 2021 (60) (remove)
Document Type
- Article (53)
- Doctoral Thesis (7)
Has Fulltext
- yes (60)
Is part of the Bibliography
- no (60)
Keywords
- RNA (3)
- SARS-CoV-2 (3)
- photochemistry (3)
- Baird's rule (2)
- G-quadruplexes (2)
- NMR (2)
- NMR spectroscopy (2)
- SiGe alloys (2)
- accessibility switch (2)
- cluster compounds (2)
- excited state aromaticity (2)
- germanium (2)
- inward proton pump (2)
- microbial rhodopsin (2)
- photolabile protecting groups (2)
- rearrangements (2)
- silicon (2)
- similarity measures (2)
- substituent effects (2)
- 1,3-diamine (1)
- 2D NMR spectroscopy (1)
- 3D electron diffraction (1)
- 5'-UTR (1)
- 9-borafluorene (1)
- Ab initio calculations (1)
- Alzheimer’s disease (1)
- Analytical chemistry (1)
- Antimicrobial resistance (1)
- Aurora kinase (1)
- Bacterial structural biology (1)
- Bindungsanalyse (1)
- Biophysical chemistry (1)
- Biopysikalische Chemie (1)
- Bärnighausen tree (1)
- B−B bonds (1)
- B−H bonds (1)
- CEST (1)
- COVID19-NMR (1)
- Catalysis (1)
- Computational biology and bioinformatics (1)
- Covid19-nmr (1)
- Cryoelectron microscopy (1)
- DFT+MBD calculations (1)
- DNA (1)
- DNA conjugate (1)
- DNA recognition (1)
- DNP (1)
- DNP in solids (1)
- Diseases (1)
- Enzyme mechanisms (1)
- Faltungsdynamik (1)
- Festkörperstruktur (1)
- G-Quadruplex (1)
- G-quadruplex binders (1)
- Image processing (1)
- Infectious diseases (1)
- Ion transport (1)
- KR2 (1)
- Kinetik (1)
- Lewis acid (1)
- MET receptor (1)
- Massenspektrometrie (1)
- NMRI (1)
- NOESY (1)
- Overhauser effect (1)
- PC12APPsw (1)
- PDF-Global-Fit (1)
- PXRD (1)
- Permeation and transport (1)
- Photochemie (1)
- Pigment Green 7 (1)
- Post-Hartree-Fock methods (1)
- Potassium channels (1)
- Pulverdiffraktometrie (1)
- R values (1)
- RNA PT (1)
- RNA cleavage (1)
- RNA modification (1)
- RNA synthesis (1)
- Rh(II) catalysis (1)
- Rietveld refinement (1)
- Röntgenstrukturanalyse (1)
- SEDDS (1)
- SL1 (1)
- SMEDDS (1)
- SNEDDS (1)
- SNP (1)
- Semi-empiricalcalculations (1)
- Silafullerane (1)
- Silane (1)
- Silole (1)
- Sodium ion pump (1)
- Solution NMR spectroscopy (1)
- Solution-state NMR (1)
- TERRA RNA (1)
- Tetrelbindung (1)
- Theoretical chemistry (1)
- X-ray crystallography (1)
- X-ray structure analysis (1)
- ab initio calculations (1)
- acetylcholine (1)
- actin (1)
- adaptor mediated recruitment (1)
- aging (1)
- anilinopyrimidine (1)
- ankyrin (1)
- aptamer (1)
- automated assignment (1)
- axon bifurcation (1)
- axon branching (1)
- benzazepinone (1)
- biophysics (1)
- bond activation (1)
- boryl anions (1)
- c-Myc (1)
- cGMP signalling (1)
- cMYC (1)
- carbazole ligands (1)
- channelrhodopsin (1)
- chemical shift assignment (1)
- chemiluminescence (1)
- chemoenzymatic synthesis (1)
- continuous rotation (1)
- copper phthalocyanine (1)
- cross-correlation functions (1)
- cyanines (1)
- cycloaddition (1)
- cysteine reactivity (1)
- deep learning (1)
- de novo design (1)
- diazo compounds (1)
- diboranes (1)
- diffusion states (1)
- digestion artifact (1)
- dorsal root ganglia (1)
- drug discovery (1)
- dynamic nuclear polarization (1)
- electron crystallography (1)
- enamides (1)
- enzyme catalysis (1)
- enzyme kinetics (1)
- erythrocyte (1)
- farnesoid X receptor (1)
- flavolignan (1)
- fluidity (1)
- folding landscapes (1)
- fragment screening (1)
- glutathione (1)
- glutathionylation (1)
- hTERT (1)
- hairpin polyamides (1)
- hippocampus (1)
- hydromethylthionine (1)
- isopropanol (1)
- itch (1)
- kinetics (1)
- leukotriene A4 hydrolase (1)
- ligand design (1)
- ligases (1)
- light control (1)
- lipid based formulation (1)
- lipid suspension (1)
- malaria (1)
- mass spectrometry (1)
- memantine (1)
- membrane proteins (1)
- membrane receptors (1)
- metallo β lactamases (1)
- microdialysis (1)
- microscopy (1)
- mitochondria (1)
- mixed valence compounds (1)
- molecular docking (1)
- molecular dynamics (1)
- multi-objective optimization (1)
- multiresistant bacteria (1)
- natural compound synthesis (1)
- neural network (1)
- nitroindoles (1)
- nitrosylation (1)
- non-alcoholic fatty liver disease (1)
- non-alcoholic steatohepatitis (1)
- nuclear receptor (1)
- nucleoside analysis (1)
- oligonucleotide (1)
- oncogene promoters (1)
- one-pot reaction (1)
- optogenetic (1)
- optogenetics (1)
- oxidative folding (1)
- pain (1)
- pair distribution function analysis (1)
- pair distribution functions (1)
- pharmacokinetics (1)
- photoacid (1)
- photocaging (1)
- photocycle (1)
- photoisomerization (1)
- phototherapeutic window (1)
- phytochromes (1)
- polymers (1)
- polypharmacology (1)
- powder data (1)
- precipitation inhibitor (1)
- protein capture (1)
- protein engineering (1)
- protein kinase inhibitor (1)
- protein-protein interactions (1)
- proton transfer (1)
- reactive oxygen species (1)
- real-time NMR spectroscopy (1)
- red light (1)
- redox chemistry (1)
- rhodopsin (1)
- ribosomal exit tunnel (1)
- rivastigmine (1)
- silibinin (1)
- silybin (1)
- single-molecule imaging (1)
- single-particle tracking (1)
- single-trajectory analysis (1)
- sodium alkoxide (1)
- solid-phase synthesis (1)
- solid-state NMR (1)
- solid-state NMR spectroscopy (1)
- solvate (1)
- somatosensory system (1)
- spinal cord (1)
- spiro compounds (1)
- stereoselective synthesis (1)
- structure determination (1)
- structure-activity relationships (1)
- subvalent compounds (1)
- sulfamide (1)
- super-SMEDDS (1)
- super-SNEDDS (1)
- supersaturating drug delivery systems (1)
- supersaturation (1)
- swelling (1)
- tetrapyrrole-binding photoreceptors (1)
- thiol inhibitors (1)
- time-resolved spectroscopy (1)
- total scattering technique (1)
- total scattering techniques (1)
- transient complex (1)
- ultrafast spectroscopy (1)
- venetoclax (1)
- virulence factor (1)
Institute
- Biochemie, Chemie und Pharmazie (60) (remove)
Nuclear magnetic resonance (NMR) spectroscopy is a powerful and popular technique for probing the molecular structures, dynamics and chemical properties. However the conventional NMR spectroscopy is bottlenecked by its low sensitivity. Dynamic nuclear polarization (DNP) boosts NMR sensitivity by orders of magnitude and resolves this limitation. In liquid-state this revolutionizing technique has been restricted to a few specific non-biological model molecules in organic solvents. Here we show that the carbon polarization in small biological molecules, including carbohydrates and amino acids, can be enhanced sizably by in situ Overhauser DNP (ODNP) in water at room temperature and at high magnetic field. An observed connection between ODNP 13C enhancement factor and paramagnetic 13C NMR shift has led to the exploration of biologically relevant heterocyclic compound indole. The QM/MM MD simulation underscores the dynamics of intermolecular hydrogen bonds as the driving force for the scalar ODNP in a long-living radical-substrate complex. Our work reconciles results obtained by DNP spectroscopy, paramagnetic NMR and computational chemistry and provides new mechanistic insights into the high-field scalar ODNP.
Coronavirus disease 2019 (COVID-19) is a global pandemic posing significant health risks. The diagnostic test sensitivity of COVID-19 is limited due to irregularities in specimen handling. We propose a deep learning framework that identifies COVID-19 from medical images as an auxiliary testing method to improve diagnostic sensitivity. We use pseudo-coloring methods and a platform for annotating X-ray and computed tomography images to train the convolutional neural network, which achieves a performance similar to that of experts and provides high scores for multiple statistical indices (F1 scores > 96.72% (0.9307, 0.9890) and specificity >99.33% (0.9792, 1.0000)). Heatmaps are used to visualize the salient features extracted by the neural network. The neural network-based regression provides strong correlations between the lesion areas in the images and five clinical indicators, resulting in high accuracy of the classification framework. The proposed method represents a potential computer-aided diagnosis method for COVID-19 in clinical practice.
Single-particle tracking enables the analysis of the dynamics of biomolecules in living cells with nanometer spatial and millisecond temporal resolution. This technique reports on the mobility of membrane proteins and is sensitive to the molecular state of a biomolecule and to interactions with other biomolecules. Trajectories describe the mobility of single particles over time and provide information such as the diffusion coefficient and diffusion state. Changes in particle dynamics within single trajectories lead to segmentation, which allows to extract information on transitions of functional states of a biomolecule. Here, mean-squared displacement analysis is developed to classify trajectory segments into immobile, confined diffusing, and freely diffusing states, and to extract the occurrence of transitions between these modes. We applied this analysis to single-particle tracking data of the membrane receptor MET in live cells and analyzed state transitions in single trajectories of the un-activated receptor and the receptor bound to the ligand internalin B. We found that internalin B-bound MET shows an enhancement of transitions from freely and confined diffusing states into the immobile state as compared to un-activated MET. Confined diffusion acts as an intermediate state between immobile and free, as this state is most likely to change the diffusion state in the following segment. This analysis can be readily applied to single-particle tracking data of other membrane receptors and intracellular proteins under various conditions and contribute to the understanding of molecular states and signaling pathways.
Translational riboswitches are cis-acting RNA regulators that modulate the expression of genes during translation initiation. Their mechanism is considered as an RNA-only gene-regulatory system inducing a ligand-dependent shift of the population of functional ON- and OFF-states. The interaction of riboswitches with the translation machinery remained unexplored. For the adenine-sensing riboswitch from Vibrio vulnificus we show that ligand binding alone is not sufficient for switching to a translational ON-state but the interaction of the riboswitch with the 30S ribosome is indispensable. Only the synergy of binding of adenine and of 30S ribosome, in particular protein rS1, induces complete opening of the translation initiation region. Our investigation thus unravels the intricate dynamic network involving RNA regulator, ligand inducer and ribosome protein modulator during translation initiation.
The Corona pandemic has painfully taught us the threat of new pathogens in a globalized world and how vital modern vaccines are. Platform technologies play an important role in the discovery of new vaccines as reducing the time for the development dramatically — time that saves lives. Here, we present the protein Dodecin and how it may be utilized as a versatile platform technology to produce cheap and robust new vaccines for everyone in all parts of the world.
The prevention of tau protein aggregations is a therapeutic goal for the treatment of Alzheimer's disease (AD), and hydromethylthionine (HMT) (also known as leucomethylthioninium-mesylate [LMTM]), is a potent inhibitor of tau aggregation in vitro and in vivo. In two Phase 3 clinical trials in AD, HMT had greater pharmacological activity on clinical endpoints in patients not receiving approved symptomatic treatments for AD (acetylcholinesterase (AChE) inhibitors and/or memantine) despite different mechanisms of action. To investigate this drug interaction in an animal model, we used tau-transgenic L1 and wild-type NMRI mice treated with rivastigmine or memantine prior to adding HMT, and measured changes in hippocampal acetylcholine (ACh) by microdialysis. HMT given alone doubled hippocampal ACh levels in both mouse lines and increased stimulated ACh release induced by exploration of the open field or by infusion of scopolamine. Rivastigmine increased ACh release in both mouse lines, whereas memantine was more active in tau-transgenic L1 mice. Importantly, our study revealed a negative interaction between HMT and symptomatic AD drugs: the HMT effect was completely eliminated in mice that had been pre-treated with either rivastigmine or memantine. Rivastigmine was found to inhibit AChE, whereas HMT and memantine had no effects on AChE or on choline acetyltransferase (ChAT). The interactions observed in this study demonstrate that HMT enhances cholinergic activity in mouse brain by a mechanism of action unrelated to AChE inhibition. Our findings establish that the drug interaction that was first observed clinically has a neuropharmacological basis and is not restricted to animals with tau aggregation pathology. Given the importance of the cholinergic system for memory function, the potential for commonly used AD drugs to interfere with the treatment effects of disease-modifying drugs needs to be taken into account in the design of clinical trials.
The formation of amyloid-β oligomers plays a key role in the onset of Alzheimer’s disease. We investigated the aggregation of amyloid-β oligomers by mass spectrometry and ion mobility spectrometry, revealing those structural properties, which lead to the formation of mature fibrils. We can show that the arrangement of the first oligomers is crucial for the topology of the resulting species, leading to the formation of non-toxic aggregates or fibrils.
Herein, we present a multi-cycle chemoenzymatic synthesis of modified RNA with simplified solid-phase handling to overcome size limitations of RNA synthesis. It combines the advantages of classical chemical solid-phase synthesis and enzymatic synthesis using magnetic streptavidin beads and biotinylated RNA. Successful introduction of light-controllable RNA nucleotides into the tRNAMet sequence was confirmed by gel electrophoresis and mass spectrometry. The methods tolerate modifications in the RNA phosphodiester backbone and allow introductions of photocaged and photoswitchable nucleotides as well as photocleavable strand breaks and fluorophores.
G-quadruplexes (G4), found in numerous places within the human genome, are involved in essential processes of cell regulation. Chromosomal DNA G4s are involved for example, in replication and transcription as first steps of gene expression. Hence, they influence a plethora of downstream processes. G4s possess an intricate structure that differs from canonical B-form DNA. Identical DNA G4 sequences can adopt multiple long-lived conformations, a phenomenon known as G4 polymorphism. A detailed understanding of the molecular mechanisms that drive G4 folding is essential to understand their ambivalent regulatory roles. Disentangling the inherent dynamic and polymorphic nature of G4 structures thus is key to unravel their biological functions and make them amenable as molecular targets in novel therapeutic approaches. We here review recent experimental approaches to monitor G4 folding and discuss structural aspects for possible folding pathways. Substantial progress in the understanding of G4 folding within the recent years now allows drawing comprehensive models of the complex folding energy landscape of G4s that we herein evaluate based on computational and experimental evidence.