A5076670773- Parkinson's Disease Mechanisms and Treatments
- Photochemistry and Electron Transfer Studies
- Alzheimer's disease research and treatments
- Photoreceptor and optogenetics research
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Photochromic and Fluorescence Chemistry
- Spectroscopy and Quantum Chemical Studies
- Luminescence and Fluorescent Materials
- Advanced Biosensing Techniques and Applications
- Radical Photochemical Reactions
- Advanced Fluorescence Microscopy Techniques
- Pancreatic function and diabetes
- Lipid Membrane Structure and Behavior
- Monoclonal and Polyclonal Antibodies Research
- Conducting polymers and applications
- Molecular Sensors and Ion Detection
- Advanced biosensing and bioanalysis techniques
- Electrochemical sensors and biosensors
- DNA and Nucleic Acid Chemistry
- Porphyrin and Phthalocyanine Chemistry
- biodegradable polymer synthesis and properties
- Free Radicals and Antioxidants
- CAR-T cell therapy research
- Diabetes and associated disorders
Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry
2016-2024
Miltenyi Biotec (Germany)
2019-2024
Czech Academy of Sciences
2019-2020
European Molecular Biology Laboratory
2013-2018
European Molecular Biology Laboratory
2018
Taras Shevchenko National University of Kyiv
2005-2016
Centre National de la Recherche Scientifique
2005-2016
Laboratoire de Biophotonique et Pharmacologie
2009-2016
Université de Strasbourg
2009-2016
European Bioinformatics Institute
2014
Cholesterol and sphingomyelin form together a highly ordered membrane phase, which is believed to play important biological functions in plasma membranes of mammalian cells. Since present mainly at the outer leaflet cell membranes, monitoring its lipid order requires molecular probes capable bind specifically this exhibit negligibly slow flip-flop. In work, such probe was developed by modifying solvatochromic fluorescent dye Nile Red with an amphiphilic anchor group. To evaluate flip-flop...
Many critical advances in research utilize techniques that combine high-resolution with high-content characterization at the single cell level. We introduce MICS (MACSima Imaging Cyclic Staining) technology, which enables immunofluorescent imaging of hundreds protein targets across a specimen subcellular resolution. is based on cycles staining, imaging, and erasure, using photobleaching fluorescent labels recombinant antibodies (REAfinity Antibodies), or release (REAlease Antibodies) their...
Parkinson disease is characterized cytopathologically by the deposition in midbrain of aggregates composed primarily presynaptic neuronal protein α-synuclein (AS). Neurotoxicity currently attributed to oligomeric microaggregates subjected oxidative modification and promoting mitochondrial proteasomal dysfunction. Unphysiological binding membranes these other organelles presumably involved. In this study, we performed a systematic determination influence charge, phase, curvature, defects,...
We introduce a sensor molecule, AS140-MFC, consisting of covalent adduct an Ala-to-Cys mutant α-synuclein with the 3-hydroxychromone dual emission dye MFC. show that AS140-MFC construct is multiparametric fluorescent probe suitable for continuous monitoring protein aggregation and sensitive to early intermediate stages aggregation, process associated Parkinson's disease.
Abstract Photoactivation of caged biomolecules has become a powerful approach to study cellular signalling events. Here we report method for anchoring and uncaging exclusively at the outer leaflet plasma membrane by employing photocleavable, sulfonated coumarin derivative. The novel caging group allows quantifying reaction progress efficiency reactions in live-cell microscopy setup, thereby greatly improving control experiments. We synthesized arachidonic acid derivatives bearing new...
Herein, the efficient interaction of an environment-sensitive fluorophore that undergoes excited-state intramolecular proton transfer (ESIPT) with DNA has been realized by conjugation a 3-hydroxychromone (3HC) polycationic spermine. On binding to double-stranded (dsDNA), ratio two emission bands 3HC conjugates changes up 16-fold, so ESIPT product increases dramatically. This suggests screening from water molecules in complex, which is probably its intercalation into dsDNA. In sharp contrast,...
We present the design, synthesis, and functional evaluation of peptide-based fluorescent constructs for wavelength-ratiometric biosensing a protein analyte. The concept was shown using high-affinity model interaction between 18 amino acid peptide pTMVP recombinant antibody fragment, Fab57P. functionalized in two different positions with 6-bromomethyl-2-(2-furanyl)-3-hydroxychromone, an environmentally sensitive fluorophore two-band emission. equilibrium dissociation constant Fab57P largely...
Interactions of the presynaptic protein α-synuclein with membranes are involved in its physiological action as well pathological misfolding and aggregation related to Parkinsons's disease. We studied conformation orientation bound model vesicular using multiparametric response polarity-sensitive fluorescent probes together CD EPR measurements. At low lipid ratio binds through N-terminal domain. When lipids excess, α-helical content role C-terminus binding increase. Highly rigid also induce a...
α-Synuclein is a neuronal protein involved in synaptic vesicle trafficking. During the course of Parkinson's disease, it aggregates, forming amyloid fibrils that accumulate midbrain. This pathological fibrillization process strongly modulated by physiological interactions α-synuclein with lipid membranes. However, detailed mechanism this effect remains unclear. In work, we used environment-sensitive fluorescent dyes to study influence model membranes on kinetics fibrillization. We observed...
3-Hydroxyquinolones undergo excited-state intramolecular proton transfer (ESIPT), resulting in a dual emission highly sensitive to H-bonding perturbations. Here, we report on the strong effect of viscosity 2-(2-thienyl)-3-hydroxyquinolone protic solvents. An increase significantly decreases formation ESIPT product, thus changing dramatically ratio two bands. Time-resolved studies suggest presence solvated species characterized by decay times close solvent relaxation viscous media. The H bond...
Fatty acids activate GPR40 and K<sup>+</sup> channels to modulate β-cell function.
The secretion of insulin from β-cells depends on extracellular factors, in particular glucose and other small molecules, some which act G-protein–coupled receptors. Fatty acids (FAs) have been discussed as exogenous secretagogues for decades, especially after the FA receptor GPR40 (G-protein–coupled 40) was discovered. However, role FAs endogenous signaling factors has not investigated until now. In present work, we demonstrate that lowering levels β-cell medium by stringent washing or...
Abstract Inorganic hydrophobically capped NPs such as quantum dots, superparamagnetic iron oxide, or gold nanoparticles can be modified to make them water‐soluble by their embedding in an amphiphilic polymer shell. This shell prefunctionalized the integration of organic fluorophores, which allows observation with fluorescence based techniques. The fluorophore could either located more hydrophobic part inner shell, on hydrophilic surface pointing towards solution. Herein we prepared decorated...
Misfolding of the protein α-synuclein (αSyn) into amyloid fibrils plays a central role in development Parkinson's disease. Most approaches for inhibition αSyn fibril formation are based on stabilizing native monomeric form or destabilizing fibrillized misfolded form. They require high concentrations inhibitor and therefore cannot be easily used therapies. In this work, we designed an (Inh-β) that selectively binds growing ends creates steric hindrance binding αSyn. This approach permits at...
Plaques of amyloid fibrils composed neuronal protein α-synuclein are one the hallmarks Parkinson's disease, and their selective imaging is crucial to study mechanism its pathogenesis. However, existing fluorescent probes for amyloids efficient only in solution tissue systems, they not enough visualization living cells. In this study, we present two molecular rotor-based RB1 RB2. These thiazolium show affinity turn-on fluorescence response upon interactions. Because extended π-conjugation...
Herein, the fluorescence properties of a series 2-aryl-3-hydroxyquinolones (3HQs) were investigated and compared with well-studied 3-hydroxyflavone. All these compounds found to display dual well-separated bands in organic solvents aqueous solutions. Using steady-state time-resolved spectroscopy, we showed that their is due an excited state intramolecular proton transfer reaction. Moreover, absorption spectra most 3HQs tested be similar, indicating they are not sensitive substituent at...
The aggregation of α-synuclein is associated with progression Parkinson's disease. We have identified submicrometer supramolecular structures that mediate the early stages overall mechanism. sequence structural transformations between metastable intermediates were captured and characterized by atomic force microscopy guided a fluorescent probe sensitive to preamyloid species. A novel ∼0.3–0.6 μm molecular assembly, denoted acuna, nucleates, expands, liberates fibers distinctive segmentation...