Institutes
Refine
Year of publication
Document Type
- Doctoral Thesis (311)
- Article (282)
- Preprint (38)
- Contribution to a Periodical (25)
- Book (18)
- Report (2)
Language
- English (521)
- German (154)
- Multiple languages (1)
Has Fulltext
- yes (676)
Is part of the Bibliography
- no (676)
Keywords
- RNA (12)
- SARS-CoV-2 (10)
- NMR spectroscopy (9)
- inflammation (9)
- photochemistry (9)
- NMR (8)
- Biochemistry (7)
- Cell biology (7)
- E2 enzyme (6)
- TRACT (6)
- X-ray crystallography (6)
- oligomerization (6)
- ubiquitination (6)
- Alzheimer’s disease (5)
- COVID19-NMR (4)
- DNA (4)
- DNA-PAINT (4)
- ISGylation (4)
- Mass spectrometry (4)
- fluorescence (4)
- neurodegeneration (4)
- optogenetics (4)
- photolabile protecting groups (4)
- rhodopsin (4)
- structural biology (4)
- Antimicrobial resistance (3)
- Biophysical chemistry (3)
- C. elegans (3)
- Cancer (3)
- Non-structural protein (3)
- PBPK (3)
- RNA structures (3)
- Schmerz (3)
- Solution NMR spectroscopy (3)
- Solution NMR-spectroscopy (3)
- acetylcholine (3)
- autophagy (3)
- drug discovery (3)
- hippocampus (3)
- machine learning (3)
- mass spectrometry (3)
- membrane proteins (3)
- microdialysis (3)
- nuclear receptor (3)
- oligonucleotides (3)
- pain (3)
- polypharmacology (3)
- solid-state NMR (3)
- 5-lipoxygenase (2)
- 5′-UTR (2)
- 6-shogaol (2)
- ABC transporter (2)
- Arzneimittel (2)
- Bacterial biofilms (2)
- Bacterial structural biology (2)
- Baird's rule (2)
- Biotechnology (2)
- Chemical tools (2)
- Chromones (2)
- Covid19-NMR (2)
- Cryoelectron microscopy (2)
- DFT (2)
- EGFR (2)
- EPR (2)
- Endothelial cells (2)
- Enzyme mechanisms (2)
- G-Quadruplex (2)
- G-quadruplexes (2)
- GABARAP (2)
- GPCR (2)
- Host-biofilm interactions (2)
- ISGlyation (2)
- Inflammation (2)
- Innate immune response (2)
- LC3 (2)
- MLL (2)
- Mechanisms of disease (2)
- Medicinal chemistry (2)
- Membrane Proteins (2)
- Membrane proteins (2)
- Metabolism (2)
- NR4A2 (2)
- NanoBRET (2)
- PROTAC (2)
- Permeation and transport (2)
- Persistent wound infections (2)
- Pharmazeutische Technologie (2)
- Pharmazie (2)
- Photochemie (2)
- Photolabile Schutzgruppen (2)
- Precipitation inhibition (2)
- Protein drugability (2)
- RNA modification (2)
- RNA processing (2)
- Rietveld refinement (2)
- SL1 (2)
- SiGe alloys (2)
- Solution-state NMR (2)
- Structural biology (2)
- Supersaturation (2)
- Ubiquitin (2)
- Wirkstofffreisetzung (2)
- Zingiber officinale Roscoe (2)
- accessibility switch (2)
- actin (2)
- adenylyl cyclases (2)
- ankyrin (2)
- aptamers (2)
- bioequivalence (2)
- boron (2)
- boryl anions (2)
- boswellic acids (2)
- click chemistry (2)
- cluster compounds (2)
- computational chemistry (2)
- cyclic nucleotide-gated channels (2)
- deep learning (2)
- dorsal root ganglia (2)
- epigenetics (2)
- erythrocyte (2)
- excited state aromaticity (2)
- farnesoid X receptor (2)
- fluorescent probes (2)
- fluorine (2)
- fragment screening (2)
- germanium (2)
- glucose (2)
- guanylyl cyclases (2)
- inward proton pump (2)
- lactate (2)
- malaria (2)
- microbial rhodopsin (2)
- microscopy (2)
- microtubule-targeting agents (2)
- mitochondrial respiration (2)
- molecular dynamics (2)
- non-alcoholic steatohepatitis (2)
- phosphorylation (2)
- photoisomerization (2)
- photolabile Schutzgruppen (2)
- protein structure (2)
- reactive oxygen species (2)
- rearrangements (2)
- receptor tyrosine kinases (2)
- silicon (2)
- similarity measures (2)
- single-particle tracking (2)
- skin infection model (2)
- spinal cord (2)
- substituent effects (2)
- subvalent compounds (2)
- super-resolution microscopy (2)
- tRNA splicing (2)
- time-resolved spectroscopy (2)
- transcription factor (2)
- tumor microenvironment (2)
- ultrafast spectroscopy (2)
- vascular endothelial cells (2)
- virulence factor (2)
- 1,3-diamine (1)
- 10-Hydroxyaloins A/B (1)
- 140Ce (1)
- 19F (1)
- 19F NMR shifts for fluoroarenes (1)
- 2'-deoxyguanosine riboswitch (1)
- 2-Photonen (1)
- 2D NMR spectroscopy (1)
- 2′-O-methylation (1)
- 3D electron diffraction (1)
- 3D reconstruction and image processing (1)
- 4-fluoroamphetamine (1)
- 5'-UTR (1)
- 5-lipoxygenase; (1)
- 9-HODE (1)
- 9-borafluorene (1)
- ABC Transporter (1)
- ABC proteins, ribosome recycling (1)
- ABC transporters (1)
- ABCE1 (1)
- ADAR (1)
- AF4 (1)
- AF4–MLL (1)
- AMP-activated kinase (AMPK) (1)
- ATG4 (1)
- ATG8 (1)
- ATP binding (1)
- ATPases (1)
- ATTO 390 (1)
- Ab initio calculations (1)
- Absorption modeling (1)
- Acute leukemia, chromosomal translocation, MLL, KMT2A, AF4-MLL, reciprocal fusion protein, MLL-r leukemia, (1)
- Acute myeloid leukemia (AML) (1)
- Adeno-associated virus vector (1)
- Adenosine A1 receptor (1)
- Age (1)
- Airport emissions (1)
- Akute lymphoblastische Leukämie (1)
- Alkylation of RNA (1)
- Aloe (1)
- Aloe lateritia ENGLER (1)
- Alterung (1)
- Alzheimer's disease (1)
- Analytical chemistry (1)
- Angiogenesis (1)
- Anthranoids (1)
- Anthraquinones (1)
- Anthrones (1)
- Antibiotic resistance (1)
- Antigen carrier (1)
- Antigen processing and presentation (1)
- Antimuscarinic and Papaverine-Like Activity (1)
- Antisense agents (1)
- Apoptosis (1)
- Aptamer (1)
- Aptamere (1)
- Arc protein (1)
- Armadillo repeat protein (1)
- Arzneimittelanalogon (1)
- Asphodelaceae (1)
- Assignment (1)
- Atg8 (1)
- Aurora kinase (1)
- Autophagy (1)
- B-cell lymphoma (1)
- BACE1 (1)
- BET proteins (1)
- BH3 mimetics (1)
- BRG1 (1)
- Bacterial Signal Transduction (1)
- Bacterial biofilm (1)
- Binding Kinetics (1)
- Binding kinetic (1)
- Bindungsanalyse (1)
- BioID (1)
- Biochemische Analyse (1)
- Bioenabling formulations (1)
- Bioenergetics (1)
- Bioequivalence (1)
- Biological techniques (1)
- Biologie (1)
- Biomaterials – proteins (1)
- Biophysics (1)
- Biophysik (1)
- Biopysikalische Chemie (1)
- Biowaiver (1)
- Bispecific (1)
- Black Lipid Membrane (1)
- Brain (1)
- Broken symmetry (1)
- Bärnighausen tree (1)
- B−B bonds (1)
- B−H bonds (1)
- CAR-immunotherapy (1)
- CEST (1)
- CNN (1)
- CNP (1)
- COVID-19 (1)
- CPVT (1)
- CRBN (1)
- CRISPR/Cas9 (1)
- CXCL13 (1)
- CXCR5 (1)
- Caenorhabditis elegans (1)
- Calcium (1)
- Calstabin2/FKBP12.6 (1)
- Cancer models (1)
- Capsule Synthesis (1)
- Carbanions (1)
- Cardiovascular disease (1)
- Catalysis (1)
- Cell division (1)
- Cell-free Protein Expression (1)
- Cell-free Protein Synthesis (1)
- Cell-free protein synthesis (1)
- Cellular microbiology (1)
- Cellular neuroscience (1)
- Cellular suicide switch (1)
- Ceramide Synthase (1)
- ChIP-Seq (1)
- Chaperones (1)
- Chemical characterization (1)
- Chemical modification (1)
- Chemie (1)
- Chemistry (1)
- Chikungunya (1)
- Chloroxospezies (1)
- Chrimson (1)
- Clinical relevant dissolution specification (1)
- Colitis assoziate colorectal cancer (1)
- Colorectal cancer (1)
- Complex I (1)
- Complex II (1)
- Computational biology and bioinformatics (1)
- Controlled freezing/thawing (1)
- Covid19-nmr (1)
- Cryo-concentration (1)
- Cryo-electron Tomography (1)
- Crystal and Molecular Structure (1)
- Curcuminoid concentrations (1)
- Cy5.5 (1)
- Cyclization (1)
- CysLTR1 (1)
- Cysteine‐Rich Domain (CRD) (1)
- DDR (1)
- DEAD-Box Helicase (1)
- DFT+MBD calculations (1)
- DNA G-quadruplex (1)
- DNA conjugate (1)
- DNA damage response (1)
- DNA methylation (1)
- DNA pulldown (1)
- DNA recognition (1)
- DNA-protein-interactions (1)
- DNP (1)
- DNP in solids (1)
- Daclatasvir (1)
- Degrader design (1)
- Designed ankyrin repeat protein (1)
- Desinfektionsmittel (1)
- DiI (1)
- Diffuse large B-cell lymphoma (1)
- Dipol (1)
- Directional freezing (1)
- Diseases (1)
- Dissolution (1)
- Dissolution nanoparticles (1)
- Disulfide bond (1)
- Disulphide Bridges (1)
- Drug Delivery (1)
- Drug delivery systems (1)
- Drug discovery (1)
- Drug screening (1)
- Drug substance bottles (1)
- Dynamics (1)
- E3 Ligase (1)
- EPR spectroscopy (1)
- ERK3 (1)
- ERQC (1)
- Efflux system (1)
- Electron Paramagnetic Resonance (1)
- Electron microscopy (1)
- Electrospinning (1)
- Elektrochemie (1)
- Enantioselektive Katalyse (1)
- Endothelial cell (1)
- Energie (1)
- Enthalpy (1)
- Entwicklungsbiologie (1)
- FAIRE-Seq (1)
- FBDD (1)
- FBS (1)
- FPR (1)
- Faltungsdynamik (1)
- Fatty acid synthases (1)
- Ferroptosis (1)
- Festkörperstruktur (1)
- Flash photolysis (1)
- Flavin homeostasis (1)
- Fluorene derivatives (1)
- Food effect (1)
- Fortpflanzung (1)
- Fragment (1)
- Freezing and thawing (1)
- Functional aspects of cell biology (1)
- Fusion proteins (1)
- G protein-coupled receptors (1)
- G-protein-coupled receptors (1)
- G-quadruplex binders (1)
- G2A receptor (1)
- GC-MS (1)
- GIIb/IIIa-receptor (1)
- Gastrointestinaltrakt (1)
- GdIr2Si2 (1)
- Gene therapy (1)
- Genetic engineering (1)
- Genetics (1)
- Genexpression (1)
- Genome engineering (1)
- Genregulation (1)
- Geschichte der Pharmazie (1)
- Glucose (1)
- Glutathione (1)
- Guanylatzyklasen (1)
- Gβγ subunit (1)
- H/ACA-RNP (1)
- HCV (1)
- HIV protease inhibitors (1)
- Haloferax volcanii (1)
- HeLa cells (1)
- Helicase (1)
- Hepatitis B virus (1)
- Herpes Simplex Virus Type 1 (HSV-1) (1)
- Heterocycles (1)
- High Performance Liquid (1)
- Histidine Kinases (1)
- Homeoviscous adaptation (1)
- Homonataloins A and B (1)
- Hydrodynamik (1)
- IAP (1)
- INS (1)
- ITGA9 (1)
- Image processing (1)
- Immune evasion (1)
- Immunochemistry (1)
- Immunology (1)
- Immunseren (1)
- In situ hybridization (1)
- In vitro wound models (1)
- Infectious diseases (1)
- Inflammatory Bowel Disease (1)
- Influenza (1)
- Innovation (1)
- Instrumentation & Devices (1)
- Ion transport (1)
- Ischämie (1)
- Isolation, separation and purification (1)
- Isothermal Titration Calorimetry (1)
- Jet engine oil (1)
- Juckreiz (1)
- Jurkat (1)
- K48-linked (1)
- K63-linked (1)
- KCNT1 (1)
- KMT2A (1)
- KR2 (1)
- Kaliumkanal (1)
- Kaliumkanal-Aktivatoren (1)
- Kd determination (1)
- Ketonkörper (1)
- Kinase (1)
- Kinase Inhibitors (1)
- Kinase inhibitors (1)
- Kinetik (1)
- Knochenmarksmikromilieu (1)
- Knotless phytochrome (1)
- LASS (1)
- LC-MS-based lipid mediator analysis (1)
- LC3/GABARAP (1)
- LILBID-MS (1)
- LIMK1 (1)
- LIMK2 (1)
- LINC00607 (1)
- LINE-1 (1)
- LIR (1)
- LIR motif (1)
- LIR motifs (1)
- Lehramt (1)
- Leukaemia (1)
- Leukemia (1)
- Leukocytes (1)
- Lewis acid (1)
- Ligands (1)
- Lipid Environment (1)
- Lipid packing (1)
- Lipidinteraktion (1)
- Lipoprotein Structure (1)
- Liposomes (1)
- M1 Ubiquitination (1)
- MACS (1)
- MAPK6 (1)
- MET (1)
- MET receptor (1)
- MFS-type tripartite system (1)
- MHC I (1)
- MLH1 (1)
- MLL-r acute leukemia (1)
- MODY (1)
- Macrodomain (1)
- Makrophagen (1)
- Massenspektrometrie (1)
- Mechanistic (1)
- Medication Appropriatness Index (1)
- Membrane Protein (1)
- Membrane fluidity (1)
- Membrane homeostasis (1)
- Membranes (1)
- Mesoporous silica (1)
- Meta effect (1)
- Metabolic Regulation (1)
- Metabolismus (1)
- Mice (1)
- Microbial Rhodopsins (1)
- Microbiology (1)
- Microdialysis (1)
- Mitochondria (1)
- Mitochondrial dysfunction (1)
- Mitosis (1)
- Modification (1)
- Molecular Interactions (1)
- Molecular Neuroscience (1)
- Molecular biology (1)
- Molecular glue (1)
- Monolage (1)
- Multi-domain proteins (1)
- Multidrug Transporters (1)
- Multimedikation / Polypharmazie (1)
- Multimorbidität (1)
- Multiphoton microscopy (1)
- Mycobacterium tuberculosis (1)
- N-glycoproteome (1)
- NADPH oxidase (1)
- NASH (1)
- NMR Solution Structure (1)
- NMR shift calculation (1)
- NMR solution structure (1)
- NMRI (1)
- NOESY (1)
- NPR2 (1)
- NR4A3 (1)
- NS5A (1)
- Nanocarriers (1)
- Nanodiscs (1)
- Nanotechnologie (1)
- Natural product (1)
- Natural products (1)
- Neuropathic pain (1)
- New E3-ligase ligands (1)
- Nox (1)
- Nox inhibition (1)
- Nucleic acid-binding domain (1)
- Nucleolar protein 14 (1)
- Nukleinsäuren (1)
- Nukleäre Rezeptoren (1)
- OTULIN (1)
- Oligonukleotid (1)
- Oncogenes (1)
- Oncoprotein activation (1)
- Ophthalmologie (1)
- Optogenetics (1)
- Organische Synthese (1)
- Organokatalyse (1)
- Orphan nuclear receptor (1)
- Outer Membrane Protein RcsF (1)
- Overhauser effect (1)
- Oxanthrone Glucosyls (1)
- Oxidative phosphorylation (1)
- PAC-1 (1)
- PBPK modelling (1)
- PBPK/PD (1)
- PC12APPsw (1)
- PDF-Global-Fit (1)
- PELDOR (1)
- PELDOR / DEER (1)
- PELDOR/DEER spectroscopy (1)
- PIM kinases (1)
- PLGA nanoparticles (1)
- PRIMUM-Studie (1)
- PXRD (1)
- Pain behavior (1)
- Paramyxoviruses (1)
- Parkinson’s disease (1)
- Partial agonist (1)
- Patch Clamp (1)
- Patch-clamp (1)
- Peptide nucleic acids (1)
- Pharmacology (1)
- Pharmazeutische Chemie (1)
- Phenalen, Heteroatom-Dotiert (1)
- Phosphoproteome (1)
- Photocages (1)
- Photochemistry (1)
- Photoisomerization (1)
- Photolabile protecting groups (1)
- Photoschalter (1)
- Photosynthesis (1)
- Physical chemistry (1)
- Physiologically Based Pharmacokinetic Modelling (1)
- Phytochrome (1)
- Pigment Green 7 (1)
- Pneumoviruses (1)
- Polyketide synthases (1)
- Polyketides (1)
- Polypeptid transport-associated domains (1)
- Post-Hartree-Fock methods (1)
- Potassium channels (1)
- Pre‐Ligand Assembly Domain (PLAD) (1)
- Process characterization (1)
- Process time (1)
- Proteasome inhibitor (1)
- Protein Kinase (1)
- Protein biosynthesis (1)
- Protein engineering (1)
- Protein folding (1)
- Protein synthesis (1)
- Proteins (1)
- Proteomics (1)
- Proteostasis (1)
- Pruritus (1)
- Pseudocontact shift (1)
- Pseudouridine (1)
- Pseudouridylation (1)
- Pulverdiffraktometrie (1)
- Puromycin (1)
- QbD (1)
- Quality control (1)
- Quantenpunkte (1)
- Quinonoids (1)
- R values (1)
- RMN (1)
- RNA PT (1)
- RNA cleavage (1)
- RNA degradation (1)
- RNA dynamics (1)
- RNA modifications (1)
- RNA synthesis (1)
- RNA therapy (1)
- RNA, biochemistry, mass spectrometry (1)
- RNA-Seq (1)
- RNA-binding proteins (1)
- RND (1)
- RXR (1)
- RXR-Selektivität (1)
- RXR-Subtypen (1)
- Rab27a (1)
- Radiotherapy (1)
- Regulation der Genexpression (1)
- Regulation of lipid metabolism (1)
- Release testing (1)
- Repair (1)
- Repression <Genetik> (1)
- Retinoid X Rezeptoren Subtypen (1)
- Retrotransposition (1)
- Rh(II) catalysis (1)
- Rhabdomyosarcoma (1)
- Rhamnus purshianus D. C. (1)
- RhlB (1)
- Rhodopsine (1)
- Ribonucleoproteins (1)
- Ribosome Recycling (1)
- Ribosome biogenesis (1)
- RyR2 (1)
- Ryanodin (1)
- Röntgenstrukturanalyse (1)
- S107 (1)
- SAR (1)
- SEDDS (1)
- SERCA (1)
- SHAPE analysis (1)
- SL5a (1)
- SL5b (1)
- SL5b + c (1)
- SL5c (1)
- SMEDDS (1)
- SNEDDS (1)
- SNP (1)
- SOFI (1)
- SPM (1)
- STED microscopy (1)
- STM (1)
- Saccharomyces cerevisiae (1)
- Schleimpilze (1)
- Screening (1)
- Selectivity (1)
- Semi-empiricalcalculations (1)
- Sexualität (1)
- Sila-Substitution (1)
- Silacyclobutenes (1)
- Silafullerane (1)
- Silane (1)
- Silole (1)
- Silylation (1)
- Single-Molecule Localization Microscopy (SMLM) (1)
- Slack (1)
- Smac mimetic (1)
- Small molecules (1)
- Sodium ion pump (1)
- Solid Oral Dosage Forms (1)
- Solid dispersion (1)
- Solubility (1)
- Spektroskopie (1)
- Sphingolipids (1)
- Sphingosinkinase 2 (1)
- Spinach (1)
- Spinlabel (1)
- Stem-cell research (1)
- Stereochemistry (1)
- Stress response (1)
- Stroke (1)
- Structural Biology (1)
- Structure refinement (1)
- Subtomogram averaging (1)
- T-cell (1)
- TBK1 (1)
- TERRA RNA (1)
- TICT (1)
- TSEN (1)
- Target validation (1)
- Taspase1 (1)
- Temperature mapping (1)
- Tetrelbindung (1)
- TgF344-AD (1)
- Theoretical chemistry (1)
- Thyroidhormone (1)
- Tiermodell (1)
- Time-resolved spectroscopy (1)
- Tissue distribution (1)
- TmRh2Si2 (1)
- Transcription factors (1)
- Transcriptional regulation (1)
- Transient absorption (1)
- Transport Drugs (1)
- Transporters (1)
- Transposon systems (1)
- Tumour-suppressor proteins (1)
- Two-component System (1)
- UBA5 (1)
- UBL (1)
- UFIM (1)
- UFM1 (1)
- ULK4 (1)
- UV/Vis spectroscopy (1)
- Ubiquitin chains (1)
- Ubiquitinome (1)
- Ultrafine particles (UFPs) (1)
- Ultrakurzzeit-Spektroskopie (1)
- Unc-51-like kinase (1)
- VHL (1)
- Viologene (1)
- Vioprolide A (1)
- Viral entry (1)
- Virologie (1)
- Virus-host Interaction (1)
- Wasserlöslichkeit (1)
- Wound dressings (1)
- Wound infection (1)
- X-ray structure analysis (1)
- Xenocoumacin (1)
- ZIKV (1)
- Zolpidem (1)
- Zolpidem; Food-effect, PBBM, PBPK (1)
- Zweiphotonen-Anregung (1)
- Zyklisierung (1)
- absolute quantification of RNA modifications (1)
- ab initio calculations (1)
- accessory proteins (1)
- actin cytoskeleton dynamics (1)
- acute leukemia (1)
- acyclovir (1)
- adaptor mediated recruitment (1)
- additive manufacturing (1)
- adenosine–arginine conjugate (1)
- aging (1)
- alternative matrices (1)
- ambiguous structures (1)
- amorphous solid dispersions (1)
- amyloid beta (1)
- amyloid precursor protein (1)
- amyloidogenesis (1)
- analgesia (1)
- analytical chemistry (1)
- angiogenesis-related cell functions (1)
- anilinopyrimidine (1)
- antibiotic resistance (1)
- antigen presentation (1)
- antigen processing (1)
- antisense technology (1)
- antiviral response (1)
- antiviral signaling (1)
- apoptosis (1)
- aptamer (1)
- arachidonic acid (AA) (1)
- arrhythmia model (1)
- astrogliosis (1)
- atropisomers (1)
- attention module (1)
- atypical MAPK kinase (1)
- automated assignment (1)
- axon bifurcation (1)
- axon branching (1)
- azo compounds (1)
- baicalein (1)
- barstar (1)
- benchmark standards (1)
- benzazepinone (1)
- benzothiazoles (1)
- big data (1)
- bilin-binding photoreceptors (1)
- bio-enabling formulations (1)
- bioavailability (1)
- bioconjugation (1)
- biomarker (1)
- biophysics (1)
- bioprinting (1)
- biorelevant dissolution (1)
- bio‐enabling formulations (1)
- bisubstrate inhibitors (1)
- body-on-a-chip (1)
- bond activation (1)
- boron heterocycles (1)
- breast milk (1)
- brightness (1)
- buchu (1)
- c-Myc (1)
- cGKI (1)
- cGMP signalling (1)
- cMYC (1)
- caged compounds (1)
- calsequestrin (1)
- cancer (1)
- cancer associated fibroblasts (1)
- canine cancer (1)
- capture (1)
- carbazole ligands (1)
- carbon direct detection (1)
- catalytic mechanism (1)
- cell cycle (1)
- cell migration (1)
- cell stress (1)
- cell-free expression (1)
- cell-free protein synthesis (1)
- cellular uptake and localization (1)
- ceramide synthase (1)
- cerium (1)
- cerumen (1)
- channelrhodopsin (1)
- charge transfer (1)
- chemical shift assignment (1)
- chemiluminescence (1)
- chemistry education (1)
- chemoenzymatic synthesis (1)
- chemogenomics (1)
- cholesterol (1)
- chronobiology (1)
- circular dichroism (1)
- classical Hodgkin lymphoma (1)
- clustering (1)
- co-crystal structure (1)
- coarse-grained simulations (1)
- cofilin (1)
- colon (1)
- combinatorial approaches (1)
- commercialization (1)
- comparative oncology (1)
- complex I (1)
- complex IV (1)
- computer-aided diagnosis (1)
- conductivity (1)
- confocal Raman microscopy (1)
- confocal microscopy (1)
- connection to nature (1)
- continuous rotation (1)
- copper phthalocyanine (1)
- correlated electrons (1)
- coumarin (1)
- coumarin 6 (1)
- covalent inhibitors (1)
- creams (1)
- cross-correlation functions (1)
- cross-section (1)
- cryo-electron microscopy (1)
- crystal structure (1)
- curcumin (1)
- cyanines (1)
- cycloaddition (1)
- cysteine reactivity (1)
- cysteine-redox regulation (1)
- cytokine (1)
- data curation (1)
- data projection (1)
- data science (1)
- de novo design (1)
- dendritic spines (1)
- denoising (1)
- de novo design (1)
- diacylglycerol kinase (1)
- dialysis (1)
- diazo compounds (1)
- diboranes (1)
- differential scanning fluorimetry (1)
- diffusion states (1)
- digestion artifact (1)
- dissolution (1)
- dopamine D2S/D3 receptor (1)
- drug abstinence (1)
- drug development (1)
- drug metabolism and distribution (1)
- drug release (1)
- drug resistance (1)
- drug targets (1)
- drug therapy (1)
- drug-likeness (1)
- dynamic nuclear polarization (1)
- dynamics (1)
- efflux pump (1)
- eicosanoid (1)
- electron beam induced deposition (1)
- electron crystallography (1)
- electron transfer system (1)
- electronic nose (1)
- elegans (1)
- enamides (1)
- end maturation (1)
- endolysosomal system (1)
- endonuclease (1)
- endoplasmic reticulum (1)
- endothelial cells (1)
- energy barriers (1)
- enolase-1 (1)
- environmental education (1)
- enzyme catalysis (1)
- enzyme kinetics (1)
- epitranscriptome (1)
- epitranscriptomics (1)
- ethnobotany (1)
- etravirine (1)
- evolution (1)
- exosomes (1)
- extracellular matrix (1)
- extract (1)
- famotidine (1)
- fatty acid (1)
- fatty acid/biosynthesis (1)
- filopodia (1)
- flavolignan (1)
- fluidity (1)
- fluorescent labeling (1)
- fluorophore (1)
- flux growth (1)
- folding landscapes (1)
- food effect (1)
- fragment-based design (1)
- fragment-based drug design (1)
- fragment-based screening (1)
- frankincense (1)
- free mRNA (1)
- fulgide (1)
- gallein (1)
- gapmers (1)
- gene expression (1)
- genetic code expansion (1)
- glucose transport (1)
- glutathione (1)
- glutathionylation (1)
- glycerophospholipid (1)
- glycolysis (1)
- green gap (1)
- guanidine riboswitch (1)
- guanidine-II riboswitch (1)
- hTERT (1)
- hairpin polyamides (1)
- heart-on-a-chip (1)
- hepatische Ketogenese (1)
- hepatocyte nuclear factor 4α (1)
- heteronuclear detection (1)
- hierarchical clustering (1)
- high content imaging (1)
- high dimensional complex data (1)
- high-throughput sequencing (1)
- histamine (1)
- histone deacetylase (1)
- histone modifications (1)
- homogeneous catalysis (1)
- human milk (1)
- human neurons (1)
- human pain models (1)
- human pharmacology (1)
- hxt0 strain (1)
- hydromethylthionine (1)
- hypoxia (1)
- iPSc (1)
- immune system (1)
- in silico tools (1)
- in vitro activities (1)
- in vivo neuroimaging (1)
- in-vitro–in-vivo correlation (1)
- infant health (1)
- information literacy (1)
- interaction partners (1)
- interest in animals (1)
- interface engineering (1)
- intracellular internalization (1)
- intrinsically disordered region (1)
- inflammatory pain (1)
- ion beam induced deposition (1)
- ionization (1)
- isopropanol (1)
- isothermal titration calorimetry (ITC) (1)
- isotope labeling (1)
- itch (1)
- kidney-on-a-chip (1)
- kinase (1)
- kinase inhibitors (1)
- kinetics (1)
- labelfree quantitative mass spectrometry (1)
- lattice-energy minimization (1)
- leucocytes (1)
- leukocyte adhesion (1)
- leukotriene (1)
- leukotriene A4 hydrolase (1)
- lichtaktivierbare Werkzeuge (1)
- ligand design (1)
- ligases (1)
- light control (1)
- light-induced polymerization (1)
- lipid (1)
- lipid based formulation (1)
- lipid metabolism (1)
- lipid suspension (1)
- lipidic cubic phase (1)
- lipidomics (1)
- liposomes (1)
- lipoxin (1)
- lipoxygenase (1)
- lipoxygenase inhibitor (1)
- liquid chromatography–mass spectrometry (1)
- liver fibrosis (1)
- liver-on-a-chip (1)
- long non-coding RNA (1)
- longitudinale Medikationsveränderung (1)
- lung cancer (1)
- lung tumor heterogeneity (1)
- lung-on-a-chip (1)
- lysosome (1)
- lysosomes (1)
- mRNA surveillance (1)
- macromolecular machines (1)
- macrophage (1)
- magnetic exchange coupling constants (1)
- magnetic resonance imaging (1)
- magnetism (1)
- main group elements (1)
- maternal diet (1)
- mature milk (1)
- meat adulteration (1)
- medicinal chemistry (1)
- medicinal plant (1)
- memantine (1)
- membrane anchor; substrate-binding protein dependent secondary transport; TRAP-associated extracytoplasmic immunogenic (TAXI); tripartite ATP-independent periplasmic (TRAP) (1)
- membrane dynamics (1)
- membrane fluidity (1)
- membrane mimics (1)
- membrane organization (1)
- membrane protein complexes (1)
- membrane receptors (1)
- membranes/fluidity (1)
- memory consolidation (1)
- metabolic sydrome (1)
- metabolomics (1)
- metallo β lactamases (1)
- metastasis (1)
- mice (1)
- micro-physiological systems (1)
- microRNA (1)
- microsomal prostaglandin E2 (1)
- mitochondria (1)
- mixed valence compounds (1)
- modeling & simulation (1)
- modeling and simulation (1)
- molecular docking (1)
- molecular electronics (1)
- molecular machines (1)
- molecular switch (1)
- molekulare Werkzeuge (1)
- multi-objective optimization (1)
- multi-target drug (1)
- multi-task learning (1)
- multicolor imaging (1)
- multidrug resistance protein 4 (1)
- multiple sclerosis (1)
- multiresistant bacteria (1)
- multispectral flow cytometry (1)
- multitarget drugs (1)
- multitasking protein (1)
- n_TOF (1)
- nanodiscs (1)
- nanomedicine (1)
- natural compound synthesis (1)
- nerve injury (1)
- neural network (1)
- neurodegenerative disorders (1)
- neuromuscular system (1)
- neuropathic pain (1)
- neuropathy (1)
- neurotropic virus (1)
- neutron (1)
- nitrogen direct detection (1)
- nitroindoles (1)
- nitrosylation (1)
- nociception (1)
- non-alcoholic fatty liver disease (1)
- non-canonical amino acid (1)
- non-coding RNAs (1)
- non-invasive imaging (1)
- non-natural nucleotide (1)
- nonstructural proteins (1)
- nuclear magnetic resonance (NMR) (1)
- nuclear magnetic resonance spectroscopy (1)
- nuclear receptor related-1 (1)
- nuclear receptor-related 1 (1)
- nucleobases (1)
- nucleophilic boron (1)
- nucleophilic substitution (1)
- nucleoside analysis (1)
- nucleosynthesis (1)
- oligonucleotide (1)
- oncogene promoters (1)
- one-dimensional convolutional neural network (1)
- one-pot reaction (1)
- optogenetic (1)
- organs-on-a-chip (1)
- osteopontin (1)
- overtaking innovation (1)
- oxidative folding (1)
- p38 (1)
- pSer domain (1)
- pair distribution function analysis (1)
- pair distribution function refinement (1)
- pair distribution functions (1)
- pancreatic cancer (1)
- peptide antibiotics (1)
- peptide loading complex (1)
- peptide transport (1)
- performance tests (1)
- peripheral injury (1)
- peroxisome prolifer ators-activated receptor-γ (1)
- phage lysis proteins (1)
- pharmacokinetics (1)
- pharmacokinetics/ pharmacodynamics (PK/PD), (1)
- pharmacological activity (1)
- pharmacophore model (1)
- phase separation (1)
- phenotypic screening (1)
- phospholipids/phosphatidylglycerol (1)
- photo-tethering (1)
- photoacid (1)
- photobleaching (1)
- photocage (1)
- photocages (1)
- photocaging (1)
- photocycle (1)
- photoschalbare (1)
- photospaltbare Linker (1)
- photoswitch (1)
- photoswitches (1)
- phototherapeutic window (1)
- phytochemical composition (1)
- phytochromes (1)
- platelets (1)
- polymers (1)
- polyubiquitin (1)
- potassium (1)
- potassium transporter (1)
- powder data (1)
- precipitation inhibitor (1)
- precursor synthesis (1)
- privileged structures (1)
- problem-based learning (1)
- proline isomerization (1)
- prostaglandin (1)
- prostaglandin E (1)
- prostaglandins (1)
- protein X-ray crystallography (1)
- protein capture (1)
- protein compartmentalization (1)
- protein engineering (1)
- protein folding (1)
- protein kinase inhibitor (1)
- protein motif (1)
- protein oxidation (1)
- protein tyrosine phosphatase (1)
- protein-protein interactions (1)
- proteins (1)
- proteostasis stress (1)
- proton transfer (1)
- pseudokinase (1)
- pseudouridylation (1)
- purification of protein complexes (1)
- quantenpunkte (1)
- quantum yield (1)
- quercetin (1)
- quinacridone (1)
- radical reactions (1)
- random forest regressor (1)
- real-time NMR spectroscopy (1)
- receptor condensates (1)
- receptor cross-interaction (1)
- receptor dynamics (1)
- red light (1)
- redox chemistry (1)
- regulatory science (1)
- release testing (1)
- resmetirom (1)
- resolution of inflammation (1)
- resolvin (1)
- respiratory chain (1)
- resveratrol (1)
- retinal (1)
- retinoid X receptor (1)
- rhabdomyosarcoma (1)
- rhodamine 123 (1)
- ribosomal exit tunnel (1)
- ribosome-associated quality control (1)
- riboswitch (1)
- ribozymes (1)
- rivastigmine (1)
- s-process (1)
- screening system (1)
- selbst-anordnende (1)
- self-assembled monolayers (1)
- self-initiated photografting and photopolymerization (1)
- semisolids (1)
- siRNAs (1)
- signal transduction (1)
- silibinin (1)
- silybin (1)
- single particle cryo-EM (1)
- single-molecule FRET (1)
- single-molecule imaging (1)
- single-molecule localization microscopy (1)
- single-particle cryoEM (1)
- single-trajectory analysis (1)
- site-directed spin labeling (1)
- site-specific labeling (1)
- skin delivery (1)
- skin-on-a-chip (1)
- smFRET (1)
- small protein (1)
- small-molecule inhibitor (1)
- smooth muscle cells (1)
- sodium alkoxide (1)
- solid-phase synthesis (1)
- solid-state NMR spectroscopy (1)
- soluble epoxide hydrolase (1)
- solution-state NMR (1)
- solvate (1)
- somatosensory system (1)
- soraphen (1)
- spiro compounds (1)
- splice-modulating oligonucleotides (1)
- stability of fluorescent label (1)
- stearic acid (1)
- stereoselective synthesis (1)
- streptozotocin (1)
- stress dependent RNA modification dynamics (1)
- structural proteins (1)
- structure determination (1)
- structure determination from powder data (1)
- structure-activity relationships (1)
- sugar transport assays (1)
- sugar transport inhibitors (1)
- sulfamide (1)
- super-SMEDDS (1)
- super-SNEDDS (1)
- supercomplex (1)
- supersaturating drug delivery systems (1)
- supersaturation (1)
- surface modification (1)
- surface-initiated polymerization (1)
- surfactant (1)
- swelling (1)
- synaptic transmission (1)
- synaptic vesicle recycling (1)
- synthase-1 (1)
- t(4;11) leukemia (1)
- tRNA (1)
- target variability (1)
- temperature jump (1)
- tetrapyrrole-binding photoreceptors (1)
- therapeutic equivalence (1)
- therapy (1)
- thermal stability (1)
- thiol inhibitors (1)
- thyroid hormone receptor (1)
- tissue distribution (1)
- tissue-plasma-ratio (1)
- toll-like receptor (1)
- topical formulations (1)
- total scattering technique (1)
- total scattering techniques (1)
- trafficking (1)
- transcription (1)
- transient complex (1)
- tumor (1)
- type 2 diabetes (1)
- ubiquitin-conjugating enzymes (1)
- umpolung (1)
- validation (1)
- vascular biology (1)
- vascular biology/endothelial cells (1)
- venetoclax (1)
- viral immune escape (1)
- virtual labeling (1)
- virus (1)
- vitamin B12 (1)
- voltage-gated proton channels (1)
- voltage-sensing domains (1)
- voltage-sensing phosphatases (1)
- weakly supervised learning (1)
- x-ray crystallography (1)
- yeast fatty acid synthase (1)
- zinc finger (1)
- zolpidem (1)
- zoo education (1)
- µ-protein (1)
Institute
- Biochemie, Chemie und Pharmazie (676)
- Präsidium (43)
- Medizin (35)
- Buchmann Institut für Molekulare Lebenswissenschaften (BMLS) (31)
- Zentrum für Biomolekulare Magnetische Resonanz (BMRZ) (30)
- Biowissenschaften (23)
- MPI für Biophysik (15)
- Physik (12)
- Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit (ZAFES) (5)
- Geowissenschaften / Geographie (4)
2-Aminobenzimidazole 10, although a weak catalyst in the monomeric state, is a successful building block for effective artificial ribonucleases. In an effort to identify new building blocks with improved catalytic potential, RNA cleavage by a variety of heterocyclic amidines and guanidines has been studied. In addition to pKa values and steric effects, the energy difference between tautomeric forms seems to be another important parameter for catalysis. This information is available from quantum chemical calculations on higher levels, but semiempirical methods are sufficient to get a first estimate. According to this assumption, imidazoimidazol 18, characterized by isoenergetic tautomeric forms, is superior to 2-aminoimidazol 6, the best candidate among the simple compounds. By far the largest effects are seen with 2-aminoperimidine 24, which rapidly cleaves RNA even in the micromolar concentration range. The impressive reactivity, however, is related to a tendency of compound 24 to form polycationic aggregates which are the actual catalysts.
2-Aminobenzimidazole 10, although a weak catalyst in the monomeric state, is a successful building block for effective artificial ribonucleases. In an effort to identify new building blocks with improved catalytic potential, RNA cleavage by a variety of heterocyclic amidines and guanidines has been studied. In addition to pKa values and steric effects, the energy difference between tautomeric forms seems to be another important parameter for catalysis. This information is available from quantum chemical calculations on higher levels, but semiempirical methods are sufficient to get a first estimate. According to this assumption, imidazoimidazol 18, characterized by isoenergetic tautomeric forms, is superior to 2-aminoimidazol 6, the best candidate among the simple compounds. By far the largest effects are seen with 2-aminoperimidine 24, which rapidly cleaves RNA even in the micromolar concentration range. The impressive reactivity, however, is related to a tendency of compound 24 to form polycationic aggregates which are the actual catalysts.
The single crystal growth of 19 different intermetallic compounds within the LnT2X2 family (with Ln = lanthanides, T = Co, Ru, Rh, Ir, and X = Si, P) is presented, by employing a high-temperature metal-flux technique. The habitus of the obtained crystals is platelet-like with the crystallographic c direction perpendicular to the surface and with individual masses between 1 and 100 mg. The magnetic properties of these crystals are characterized by magnetization, heat-capacity, and resistivity measurements. These crystals form the materials basis for a thorough study of exciting surface properties by angle-resolved photoemission spectroscopy.
In dieser Arbeit wird sowohl das Potenzial von molekularen Photoschaltern als lichtempfindliche Komponenten für photopharmakologische Anwendungen als auch das von künstlichen RNA-Aptameren als regulatorische Schalteinheiten für die Entwicklung von funktionellen Riboschaltern untersucht. Verschiedene wesentliche Aspekte beider Anwendungs-felder wurden eingehend einzeln untersucht und die beiden Schaltsysteme schließlich durch das Design eines synthetischen RNA-Aptamers kombiniert, dessen Ligandbindung durch licht-induzierte Isomerisierung seines Photoschalterliganden reguliert werden kann.
Molekulare Photoschalter wie Azobenzole und Spiropyrane haben sich als vielversprechende photochemische Werkzeuge erwiesen, um lichtgesteuert reversible und biochemisch nutzbare Effekte erzeugen. Spiropyrane bergen aufgrund der drastischen Veränderungen ihrer molekularen Eigenschaften infolge der Photoisomerisierung zum Merocyanin (MC) ein enormes Anwendungs-potenzial. Von den hier untersuchten wasserlöslichen Pyridin- (Py-) und Nitro-BIPS-Derivaten zeigt insbesondere die Py-BIPS-Verbindung 2 ein außerordentlich vielseitiges Verhalten. Im Vergleich zu anderen Vertretern dieser Photoschalterklasse wird ein deutlich höherer MC-Anteil von etwa 50% thermisch innerhalb von wenigen Minuten akkumuliert. Durch lichtinduzierten Ringschluss zum reinen Spiropyran (SP) und thermische Wiederherstellung des Gleichgewichts, kann diese hohe Schaltamplitude über mehrere Zyklen ohne signifikante Zersetzung beibehalten werden. Der Einsatz von schädlichem UV-Licht kann somit vermieden werden, was zusätzlich sehr vorteilhaft für einen möglichen Einsatz in einem biochemischen Kontext ist.
Verbindung 2 weist zudem mehrere Protonierungsstellen auf, die ihr in Abhängigkeit des pH-Wertes faszinierende photosaure Eigenschaften verleihen. Das einfach protonierte HMC Isomer ermöglicht eine lichtstimulierte reversible Kontrolle des pH-Wertes in einem Bereich von etwa 4,5 bis 7,5, mit möglichen pH-Sprüngen von bis zu 1,5 Einheiten. Durch transiente Absorptionsstudien wurde ein Mechanismus für die Protonenfreisetzung nachgewiesen, der lediglich auf der Veränderung des pKs-Wertes der N-protischen Position infolge des lichtinduzierten Ringschlusses beruht. Im Gegensatz dazu wird das phenolische Proton des doppelt protonierten HMCH Isomers innerhalb von 1-2 Pikosekunden nach Anregung aus dem angeregten Zustand an das Lösemittel übertragen. Durch eingehende Ultrakurzzeitmessungen der Freisetzung des phenolischen Protons, konnten die protonierten Spezies der Py- und Nitro-Merocyanine als Superphotosäuren etabliert werden. Sie können somit als ultraschnelle Auslöser für protonenvermittelte Prozesse eingesetzt werden, die zu den fundamentalsten Reaktionen in der Natur gehören.
Was potenzielle pharmakologische Zielsysteme betrifft, so dürfte RNA eine große Zukunft bevorstehen, da sie einfach zu synthetisieren ist und Zugang zu verschiedenen Ebenen zellulärer Regulationsmechanismen bietet. Insbesondere RNA-Aptamere, die in der Lage sind, niedermolekulare Liganden mit außergewöhnlich hoher Affinität und Spezifität zu binden, sind für die Entwicklung von künstlichen Riboschaltern hoch interessant. Während künstliche Aptamere für beliebige Liganden durch einen in vitro Selektionsprozess generiert werden können, ist nicht zur Gänze geklärt warum nur wenige von ihnen als aktive in vivo Riboschalter funktionieren. Die vorliegenden Ergebnisse zeigen die Bedeutung der konformationellen Aptamerdynamik während der Ligandenbindung für das Regulationspotential. Die Mg2+-abhängigen Bindungsstudien des hochfunktionellen Tetrazyklin (TC) -Aptamers zeigen, dass zweiwertige Kationen nicht nur für die korrekte Vorfaltung des Aptamers wichtig sind, sondern auch an der Ligandenbindung und RNA-Strukturanpassung selbst beteiligt sein können. Nach der Assoziation von TC an die Bindungstasche pflanzt sich eine Konformationsanpassung zur entfernten Dreifachhelixregion fort, wo Mg2+ zusätzlich für die Ausbildung endgültig gebundenen Zustandes benötigt wird.
Neben dem Einfluss von Mg2+, zeigen zeitaufgelöste Ligandenbindungsstudien von drei Ciprofloxacin (CFX) -Aptameren eine klare Korrelation zwischen der Kinetik des Struktur-anpassungsschrittes der RNA an den Liganden und dem beobachteten Regulationspotenzial in parallel durchgeführten in vivo Assays. Es wird geschlussfolgert, dass eine beschleunigte und irreversible RNA-Anpassung auf eine Konformationsänderung hindeutet, die ausgeprägt genug ist, um eine Aktivität als Riboschalter zu ermöglichen. Diese Erkenntnisse werden durch die berichteten Ligandenbindungskinetiken von anderen künstlichen Aptameren und auch von natürlichen Riboschaltern bestätigt und sollten weitreichende Implikationen für die Optimierung von Selektionsprotokollen für funktionelle Aptamere haben.
Schließlich wird ein lichtempfindliches RNA-Aptamer vorgestellt, dessen Ligand auf dem Antibiotikum Chloramphenicol (Cm) basiert, welches synthetisch mit einem Azobenzolfragment versehen wurde (azoCm). Durch systematische Optimierung von in vitro Selektionsprotokollen und die erfolgreiche Implementierung eines Belichtungsschrittes zur Isomerisierung des Liganden konnten Aptamere erhalten werden, die spezifisch an die trans-Form von azoCm binden. Bindungsaffinitätsstudien bestätigen diese Selektivität und durch Zirkulardichroismusstudien konnte zudem eine lichtinduzierte reversible Dissoziation des von cis-azoCm gezeigt werden. Damit wird hier eine erfolgreiche Entwicklungsstrategie für lichtabhängige RNA-Aptamer – Ligandsysteme dargelegt, welche wiederum fundamental neuartige Ansätze für die Erschließung lichtstimulierter biologischer Regulationswege zugänglich machen.
An automated NMR chemical shift assignment algorithm was developed using multi-objective optimization techniques. The problem is modeled as a combinatorial optimization problem and its objective parameters are defined separately in different score functions. Some of the heuristic approaches of evolutionary optimization are employed in this problem model. Both, a conventional genetic algorithm and multi-objective methods, i.e., the non-dominated sorting genetic algorithms II and III (NSGA2 and NSGA3), are applied to the problem. The multi-objective approaches consider each objective parameter separately, whereas the genetic algorithm followed a conventional way, where all objectives are combined in one score function. Several improvement steps and repetitions on these algorithms are performed and their combinations are also created as a hyper-heuristic approach to the problem. Additionally, a hill-climbing algorithm is also applied after the evolutionary algorithm steps. The algorithms are tested on several different datasets with a set of 11 commonly used spectra. The test results showed that our algorithm could assign both sidechain and backbone atoms fully automatically without any manual interactions. Our approaches could provide around a 65% success rate and could assign some of the atoms that could not be assigned by other methods.
An accurate measurement of the 140Ce(n,γ) energy-dependent cross-section was performed at the n_TOF facility at CERN. This cross-section is of great importance because it represents a bottleneck for the s-process nucleosynthesis and determines to a large extent the cerium abundance in stars. The measurement was motivated by the significant difference between the cerium abundance measured in globular clusters and the value predicted by theoretical stellar models. This discrepancy can be ascribed to an overestimation of the 140Ce capture cross-section due to a lack of accurate nuclear data. For this measurement, we used a sample of cerium oxide enriched in 140Ce to 99.4%. The experimental apparatus consisted of four deuterated benzene liquid scintillator detectors, which allowed us to overcome the difficulties present in the previous measurements, thanks to their very low neutron sensitivity. The accurate analysis of the p-wave resonances and the calculation of their average parameters are fundamental to improve the evaluation of the 140Ce Maxwellian-averaged cross-section.
The new class of microbial rhodopsins, called xenorhodopsins (XeRs),[1] extends the versatility of this family by inward H+ pumps.[2–4] These pumps are an alternative optogenetic tool to the light-gated ion channels (e.g. ChR1,2), because the activation of electrically excitable cells by XeRs is independent from the surrounding physiological conditions. In this work we functionally and spectroscopically characterized XeR from Nanosalina (NsXeR).[1] The photodynamic behavior of NsXeR was investigated on the ps to s time scale elucidating the formation of the J and K and a previously unknown long-lived intermediate. The pH dependent kinetics reveal that alkalization of the surrounding medium accelerates the photocycle and the pump turnover. In patch-clamp experiments the blue-light illumination of NsXeR in the M state shows a potential-dependent vectoriality of the photocurrent transients, suggesting a variable accessibility of reprotonation of the retinal Schiff base. Insights on the kinetically independent switching mechanism could furthermore be obtained by mutational studies on the putative intracellular H+ acceptor D220.
Photoactivatable compounds for example photoswitches or photolabile protecting groups (PPGs, photocages) for spatiotemporal light control, play a crucial role in different areas of research. For each application, parameters such as the absorption spectrum, solubility in the respective media and/or photochemical quantum yields for several competing processes need to be optimized. The design of new photochemical tools therefore remains an important task. In this study, we exploited the concept of excited-state-aromaticity, first described by N. Colin Baird in 1971, to investigate a new class of photocages, based on cyclic, ground-state-antiaromatic systems. Several thio- and nitrogen-functionalized compounds were synthesized, photochemically characterized and further optimized, supported by quantum chemical calculations. After choosing the optimal scaffold, which shows an excellent uncaging quantum yield of 28 %, we achieved a bathochromic shift of over 100 nm, resulting in a robust, well accessible, visible light absorbing, compact new photocage with a clean photoreaction and a high quantum product (ϵ⋅Φ) of 893 M−1 cm−1 at 405 nm.
The new class of microbial rhodopsins, called xenorhodopsins (XeRs),[1] extends the versatility of this family by inward H+ pumps.[2–4] These pumps are an alternative optogenetic tool to the light-gated ion channels (e.g. ChR1,2), because the activation of electrically excitable cells by XeRs is independent from the surrounding physiological conditions. In this work we functionally and spectroscopically characterized XeR from Nanosalina (NsXeR).[1] The photodynamic behavior of NsXeR was investigated on the ps to s time scale elucidating the formation of the J and K and a previously unknown long-lived intermediate. The pH dependent kinetics reveal that alkalization of the surrounding medium accelerates the photocycle and the pump turnover. In patch-clamp experiments the blue-light illumination of NsXeR in the M state shows a potential-dependent vectoriality of the photocurrent transients, suggesting a variable accessibility of reprotonation of the retinal Schiff base. Insights on the kinetically independent switching mechanism could furthermore be obtained by mutational studies on the putative intracellular H+ acceptor D220.
Redirection of the transcription factor SP1 to AT rich binding sites by a synthetic adaptor molecule
(2021)
The ubiquitous transcription factor SP1 binds to a GC rich consensus sequence. Here we describe an adaptor molecule that mediates binding of SP1 to a non-cognate DNA site rich in AT. The adaptor is comprised of a Dervan-type hairpin polyamide with high affinity to an AT rich hexamer duplex. It also carries a 27mer DNA that contains the SP1 consensus sequence. The synthesis and purification of the polyamide-DNA conjugate is reported. Pulldown experiments and western blot analysis demonstrate adaptor mediated binding of SP1 to the hexamer duplex TTGTTA.
Photoactivatable compounds for example photoswitches or photolabile protecting groups (PPGs, photocages) for spatiotemporal light control, play a crucial role in different areas of research. For each application, parameters such as the absorption spectrum, solubility in the respective media and/or photochemical quantum yields for several competing processes need to be optimized. The design of new photochemical tools therefore remains an important task. In this study, we exploited the concept of excited-state-aromaticity, first described by N. Colin Baird in 1971, to investigate a new class of photocages, based on cyclic, ground-state-antiaromatic systems. Several thio- and nitrogen-functionalized compounds were synthesized, photochemically characterized and further optimized, supported by quantum chemical calculations. After choosing the optimal scaffold, which shows an excellent uncaging quantum yield of 28 %, we achieved a bathochromic shift of over 100 nm, resulting in a robust, well accessible, visible light absorbing, compact new photocage with a clean photoreaction and a high quantum product (ϵ⋅Φ) of 893 M−1 cm−1 at 405 nm.
Internationale Fachkonferenz im Hybrid-Format : Nachbericht zur Frankfurt Cancer Conference 2021
(2021)
Diese Arbeit ist ein detaillierter Bericht über die Forschungsaktivitäten, die ich während meiner Promotion am Max-Planck-Institut für Biophysik durchgeführt habe. Mit dem Aufkommen der direkten Elektronendetektoren erlebte die Transmissionselektronenmikroskopie von gefrorenen hydratisierten Proben (Kryo-EM) einen epochalen Wandel, die sogenannte “Auflösungsrevolution”. Ab den 2010er Jahren ermöglichte die Kommerzialisierung der ersten direkten Detektoren die Erforschung biologischer Phänomene in beispiellosem Detail und machte Kryo-EM zu einer der leistungsstärksten (und gefragtesten) Forschungsmethoden in den Biowissenschaften. Meine Forschung konzentrierte sich auf die Verwendung der Elektronen-Kryotomographie, um zwei herausfordernde Ziele zu erreichen. Das erste bestand darin, die Denaturierung von Proteinen an der Luft-Wasser-Grenzfläche zu untersuchen, und das zweite die molekulare Landschaft eines lichtempfindlichen Chloroplastenvorläufers, des Etioplasten, zu beschreiben. Um die Relevanz, Herausforderungen und Auswirkungen meiner Arbeit zu vermitteln, habe ich diese Arbeit in drei Kapitel unterteilt.
Kapitel eins enthält eine Einführung in die Transmission-Elektronenmikroskopie.
Nach einer kurzen Zusammenfassung der historischen Meilensteine in der Disziplin beschreibe ich die wesentlichen Komponenten des TEM und deren Funktionsweise. Hier lege ich besonderen Wert auf die Struktur elektromagnetischer Linsensysteme, wie sie den Weg der Elektronen beim Durchlaufen der Säule beeinflussen und wie Bilder entstehen. Der hardwarebezogene Teil der Einführung wird durch eine vereinfachte Beschreibung der Elektronendetektoren abgeschlossen, in der ich die revolutionären Aspekte der direkten Elektronendetektoren, mit der Struktur und Funktion von CCD-Detektoren (Charge Coupled Device detector) vergleiche. Als nächstes konzentriere ich mich auf die theoretischen Prinzipien der Bilderzeugung. Um die Hauptphänomene im Zusammenhang mit der Bildqualität in TEM hervorzuheben, stelle ich grundlegende Konzepte wie den Einfluss von Elektronenenergie und optischen Aberrationen vor, gefolgt von einer ausführlicheren Beschreibung des Ursprungs von Kontrast und Rauschen. Der Unterabschnitt schließt mit einigen Überlegungen darüber, wie - und vor allem wie effizient - Detektoren kontinuierliche Elektronenwellen in diskrete Bereiche (Pixel) abtasten. Der folgende Unterabschnitt ist der Erfassung und Verarbeitung tomografischer Daten gewidmet. Hier gebe ich eine vereinfachte Beschreibung, wie Kippserien mit dem Mikroskop erfasst werden und wie die Rohdaten zu einer dreidimensionalen Darstellung der Probe verarbeitet werden. Der Einfluss der Neigungsgeometrie und der Dosisverteilung auf die Rekonstruktionsqualität wird ebenfalls diskutiert. Der zweite Teil des Unterabschnitts befasst sich mit der Strukturbestimmung durch Subtomogramm-Mittelung und der Errechnung der Auflösung von Kryo-EM-Rekonstruktion. Zuletzt schließe ich das Kapitel mit einer Beschreibung der Vorbereitung biologischer Proben für die Kryo-EM-Bildgebung mit einigen abschließenden Bemerkungen zur Dynamik und den Grenzen der Vitrifizierung ab.
Kapitel zwei folgt dem Thema der Kryo-Präparation biologischer Proben mit der Untersuchung der Denaturierung von Proteinen an der Luft-Wasser-Grenzfläche.
Im Einführungsabschnitt skizziere ich die wichtigsten Aspekte dieses Phänomens. Frühe Experimente zum Verhalten von Proteinen in Lösung zeigten ihre Neigung, aus der Lösung zu ihrer Grenzfläche mit der Atmosphäre zu diffundieren. Hier bilden sie meist unlösliche Schichten denaturierter Fibrillen Es wurde vorgeschlagen, dass die Korrelation zwischen Proteindenaturierung und Kontakt mit der Grenzfläche auf einen allmählichen Entfaltungsprozess zurückzuführen ist, bei dem Tausende von Wechselwirkungen pro Sekunde zu einer immer größeren strukturellen Schädigung führen würden. Ein direkter Beweis für diesen Mechanismus wurde jedoch nie dokumentiert. Um einen tieferen Einblick in die Dynamik an der Luft-Wasser-Grenzfläche zu erhalten, sammelte ich Kryotomogramme vitrifizierter Präparate der Fettsäuresynthase (FAS, Fatty Acid Synthase) aus Hefe. Im ersten Unterabschnitt der Ergebnisse beschreibe ich, wie die biochemische und Negativkontrastierung-TEM-Analyse von FAS-Fraktionen zeigte, dass der Komplex während des gesamten Reinigungsverfahrens intakt und katalytisch aktiv blieb. Nach der Vitrifizierung ergab die Einzelpartikelanalyse jedoch, dass 90% aller Komplexe stark beschädigt waren. Die tomographische Rekonstruktion derselben Proben zeigte, dass alle FAS-Komplexe an die Luft-Wasser-Grenzfläche gebunden waren. Die Seite des Moleküls, die der Grenzfläche ausgesetzt war, schien abgeflacht zu sein, während die Seite, in der wässrigen Phase, ihre native Struktur beibehielt. Die Mittelung der Subtomogramme bestätigte, dass eine Seite von fast 90% der Partikel stark beschädigt war. Durch den Vergleich der Ausrichtung dieser beschädigten Seite mit der Position eines Rechenmodells der Luft-Wasser-Grenzfläche konnte ich nachweisen, dass sie perfekt übereinstimmen, was den ersten direkten Beweis dafür liefert, dass die Wechselwirkung mit der Luft-Wasser-Grenzfläche die lokale Denaturierung großer Proteinkomplexe herbeiführt.
...