A5008980753- Photochromic and Fluorescence Chemistry
- Photoreceptor and optogenetics research
- Microtubule and mitosis dynamics
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Redox biology and oxidative stress
- Click Chemistry and Applications
- Nanoplatforms for cancer theranostics
- Sulfur Compounds in Biology
- Advanced Fluorescence Microscopy Techniques
- Cancer therapeutics and mechanisms
- Advanced biosensing and bioanalysis techniques
- Cellular Mechanics and Interactions
- Retinal Development and Disorders
- Organoselenium and organotellurium chemistry
- Photosynthetic Processes and Mechanisms
- Ubiquitin and proteasome pathways
- Crystallography and molecular interactions
- Chemical Synthesis and Analysis
- Synthesis and Catalytic Reactions
- Cellular transport and secretion
- Protein Degradation and Inhibitors
- Molecular Sensors and Ion Detection
- Nitric Oxide and Endothelin Effects
- Supramolecular Chemistry and Complexes
TU Dresden
2024-2025
LMU Klinikum
2021-2024
Ludwig-Maximilians-Universität München
2015-2024
Kyonggi University
2023
Minzu University of China
2023
Qujing Normal University
2023
Sun Yat-sen University
2023
Leibniz University Hannover
2023
Idorsia (Switzerland)
2023
Max Planck Institute of Colloids and Interfaces
2023
How microtubules organize in embryos Cell functions ranging from cell division to morphogenesis rely on microtubules, with microtubule-organizing centers serving as anchoring sites for their outgrowth. Although the centrosome organizes microtubule cytoskeleton most animal cells, this organelle is absent early development. Using live-cell imaging, Zenker et al. found that cells of mouse embryo are connected by stable bridges direct growth within them. Microtubules emanating help guide...
Cells navigating through complex tissues face a fundamental challenge: while multiple protrusions explore different paths, the cell needs to avoid entanglement. How surveys and then corrects its own shape is poorly understood. Here, we demonstrate that spatially distinct microtubule dynamics regulate amoeboid migration by locally promoting retraction of protrusions. In migrating dendritic cells, local depolymerization within remote from organizing center triggers actomyosin contractility...
Cell-permeable photoswitchable small molecules, termed optojasps, are introduced to optically control the dynamics of actin cytoskeleton and cellular functions that depend on it. These light-dependent effectors were designed from F-actin-stabilizing marine depsipeptide jasplakinolide by functionalizing them with azobenzene photoswitches. As demonstrated, optojasps can be employed cell viability, motility, cytoskeletal signaling high spatial temporal resolution light affords. Optojasps...
Small molecule inhibitors are prime reagents for studies in microtubule cytoskeleton research, being applicable across a range of biological models and not requiring genetic engineering. However, traditional chemical cannot be experimentally applied with spatiotemporal precision suiting the length time scales inherent to microtubule-dependent cellular processes. We have synthesised photoswitchable paclitaxel-based stabilisers, whose binding is induced by photoisomerisation their metastable...
Photoswitchable reagents are powerful tools for high-precision studies in cell biology. When these globally administered yet locally photoactivated two-dimensional (2D) cultures, they can exert micron- and millisecond-scale biological control. This gives them great potential use biologically more relevant three-dimensional (3D) models
Druglike small molecules with photoswitchable bioactivity-photopharmaceuticals-allow biologists to perform studies exquisitely precise and reversible, spatial temporal control over critical biological systems inaccessible genetic manipulation. The photoresponsive pharmacophores disclosed have been almost exclusively azobenzenes, which has limited the structural substituent scope of photopharmacology. More detrimentally, for azobenzene reagents, it is not researchers' needs adapted...
α-Synuclein is a presynaptic protein the function of which has yet to be identified, but its neuronal content increases in patients synucleinopathies including Parkinson9s disease. Chronic overexpression α-synuclein reportedly expresses various phenotypes synaptic dysfunction, primary target toxicity not been determined. To investigate this, we acutely loaded human recombinant or pathological mutants their monomeric forms into calyces Held terminals slices from auditorily mature and immature...
We report the first cellular application of emerging near-quantitative photoswitch pyrrole hemithioindigo, by rationally designing photopharmaceutical PHTub inhibitors cytoskeletal protein tubulin. PHTubs allow simultaneous visible-light imaging and photoswitching in live cells, delivering cell-precise photomodulation microtubule dynamics, photocontrol over cell cycle progression death. This is acute use a hemithioindigo for high-spatiotemporal-resolution biological control cells. It...
The cyclic five-membered disulfide 1,2-dithiolane has been widely used in chemical biology and redox probes. Contradictory reports have described it either as nonspecifically reduced cells, or else a highly specific substrate for thioredoxin reductase (TrxR). Here we show that probes, such "TRFS" are by thiol reductants redox-active proteins, their cellular performance is barely affected TrxR inhibition knockout. Therefore, results of imaging inhibitor screening using 1,2-dithiolanes should...
Selectively labeling cells with damaged membranes is needed not only for identifying dead in culture, but also imaging membrane barrier dysfunction pathologies vivo. Most permeability stains are permanently colored or fluorescent dyes that need washing to remove their non-uptaken extracellular background and reach good image contrast. Others DNA-binding environment-dependent fluorophores, which lack design modularity, have potential toxicity, can detect permeabilization of cell volumes...
We report piperazine-fused six-membered-cyclic disulfides as redox substrates that unlock best-in-class bioreduction probes for live cell biology, since their self-immolation after reduction is unprecedentedly rapid. develop scalable, diastereomerically pure, six-step syntheses access four key cis- and trans-piperazine-fused cyclic dichalcogenides without chromatography. Fluorogenic using the disulfide piperazines are activated >100-fold faster than prior art monoamines, allowing us to...
Background: Hemithioindigo is a promising molecular photoswitch that has only recently been applied as photoswitchable pharmacophore for control over bioactivity in cellulo. Uniquely, contrast to other photoswitches have biology, the pseudosymmetric hemithioindigo scaffold allowed creation of both dark-active and lit-active photopharmaceuticals same binding site by priori design. However, potency previous not optimal their translation biological models. Results: Inspired structure...
Specialized cellular networks of oxidoreductases coordinate the dithiol/disulfide-exchange reactions that control metabolism, protein regulation, and redox homeostasis. For probes to be selective for enzymes effector proteins (nM μM concentrations), they must also able resist non-specific triggering by ca. 50 mM background non-catalytic monothiols. However, no such reduction-sensing systems have yet been established. Here, we used rational structural design independently vary thermodynamic...
Integrins are cell surface proteins responsible for motility. Inspired by the rich disulfide exchange chemistry of integrins, we show here inhibition migration cascade exchangers (CAXs), which also enable and inhibit penetration thiol-mediated uptake. Fast-moving CAXs such as reversible Michael acceptor dimers, dithiabismepanes, bioinspired epidithiodiketopiperazines best, much better than Ellman's reagent. The implication that integrins participate in uptake is confirmed reduced...
Azobenzene molecular switches are widely used to photocontrol material properties, and biological activity in cell culture, via photoisomerisation between E Z isomers. However, because population photoswitching is incomplete, their dynamic range of property control often small; they cannot be operated with red/NIR light, usually not applicable deep tissue. Here, we demonstrate a general method for efficient single-photon azobenzenes, glutamate receptor activity, at >700 nm live We use...
A robust, modular fluorogenic probe system has been developed which allows the highly sensitive off-ON detection of aminopeptidase activity by releasing an exceptionally photostable, insoluble, phenolic ESIPT fluorophore. The probes generate no false positive signal in over 24 hours, but when activated give a within 10 minutes.
Small-molecule prodrug approaches that can activate cancer therapeutics selectively in tumors are urgently needed. Here, we developed the first antitumor prodrugs designed for activation by thiol-manifold oxidoreductases, targeting thioredoxin (Trx) system. The Trx system is a critical cellular redox axis tightly linked to dysregulated redox/metabolic states cancer, yet it cannot be addressed current bioreductive prodrugs, which mainly cluster around oxidized nitrogen species. We instead...
Abstract Optoacoustic (or photoacoustic) imaging promises micron‐resolution noninvasive bioimaging with much deeper penetration (>cm) than fluorescence. However, optoacoustic of enzyme activity would require loud, photostable, NIR‐absorbing molecular contrast agents, which remain unknown. Most organic agents are repurposed fluorophores, severe shortcomings photoinstability or phototoxicity under imaging, as consequences their slow S 1 →S 0 electronic relaxation. We now report that known...
The regulation of ion transport across biological membranes using light is a powerful research tool with potential therapeutic applications. Microbial channelrhodopsins, widely used in optogenetics, enable passive photocurrents that facilitate advanced studies synaptic plasticity and neuronal connectivity. However, their applicability limited by the need for genetic transfection to introduce channelrhodopsins into target cells. Here, we present synthetic alternative combining small-molecule...