A5031410622- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Nuclear Structure and Function
- Advanced biosensing and bioanalysis techniques
- Telomeres, Telomerase, and Senescence
- Protein Degradation and Inhibitors
- Fluorine in Organic Chemistry
- RNA Interference and Gene Delivery
- Gold and Silver Nanoparticles Synthesis and Applications
- Synthesis and Characterization of Heterocyclic Compounds
- Peptidase Inhibition and Analysis
- interferon and immune responses
- Nanocluster Synthesis and Applications
- Muscle Physiology and Disorders
- Galectins and Cancer Biology
- Force Microscopy Techniques and Applications
- Heat shock proteins research
- RNA and protein synthesis mechanisms
- Cardiomyopathy and Myosin Studies
- Cancer Cells and Metastasis
- Synthesis and Catalytic Reactions
- Nanoparticles: synthesis and applications
Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry
2016-2025
Czech Academy of Sciences
2006-2025
Czech Academy of Sciences, Institute of Molecular Genetics
2010-2019
Czech Academy of Sciences, Institute of Experimental Medicine
2006
The development of fluorogenic reactions which lead to the formation fluorescent products from two nonfluorescent starting materials is highly desirable, but challenging. Reported herein a new concept product upon inverse electron-demand Diels-Alder reaction 1,2,4,5-tetrazines with particular trans-cyclooctene (TCO) isomers. In sharp contrast known reagents presented chemistry leads rapid unprecedented 1,4-dihydropyridazines so that fluorophore built directly chemical reaction. Attachment an...
RNA polymerase I (Pol I) transcription is essential for the cell cycle, growth, and overall protein synthesis in eukaryotes. We found that phosphatidylinositol 4,5-bisphosphate (PIP2) a part of complex on active ribosomal promoter during transcription. PIP2 makes with Pol factor UBF nucleolus. depletion reduces which can be rescued by addition exogenous PIP2. In addition, also binds directly to pre-rRNA processing factor, fibrillarin (Fib), co-localizes nascent transcripts binding Fib...
Fluorescent probes that light-up upon reaction with complementary bioorthogonal reagents are superior tools for no-wash fluorogenic bioimaging applications. In this work, a thorough study is presented on set of seventeen structurally diverse coumarin-tetrazine produce fluorescent dyes exceptional turn-on ratios when reacted trans-cyclooctene (TCO) and bicyclononyne (BCN) dienophiles. general, formation the fully aromatic pyridazine-containing resulting from BCN was found in terms...
The development of reagents that can selectively react in complex biological media is an important challenge. Here we show N1-alkylation 1,2,4-triazines yields the corresponding triazinium salts, which are three orders magnitude more reactive reactions with strained alkynes than parent 1,2,4-triazines. This powerful bioorthogonal ligation enables efficient modification peptides and proteins. positively charged N1-alkyl salts exhibit favorable cell permeability, makes them superior for...
Background Nuclear myosin I (NM1) was the first molecular motor identified in cell nucleus. Together with nuclear actin, they participate crucial events such as transcription, chromatin movements, and remodeling. NM1 is an isoform of 1c (Myo1c) that earlier known to act cytoplasm. differs from "cytoplasmic" only by additional 16 amino acids at N-terminus molecule. This acid stretch therefore suggested direct into Methodology/Principal Findings We investigated mechanism import detail. Using...
1,2,4-Triazines have recently been identified as versatile dienes participating in the inverse electron-demand Diels-Alder reaction with strained dienophiles. However, their widespread utility bioconjugation reactions is still limited. Herein, we report a systematic study on reactivity of various 1,2,4-triazines trans-cyclooctenes showing that structure both triazine and dienophile significantly affect rate. Our kinetic led to discovery novel cationic superior properties for reactions. We...
Nuclear myosin I (NM1) is a nuclear isoform of the well-known "cytoplasmic" Myosin 1c protein (Myo1c). Located on 11(th) chromosome in mice, NM1 results from an alternative start transcription Myo1c gene adding extra 16 amino acids at N-terminus. Previous studies revealed its roles RNA Polymerase and II transcription, chromatin remodeling, chromosomal movements. Its localization signal localized middle molecule therefore directs both isoforms to nucleus.In order trace specific functions...
Fluorogenic bioorthogonal reactions enable visualization of biomolecules with excellent signal-to-noise ratio. A bicyclononyne-tetrazine ligation that produces fluorescent pyridazine products has been developed. In stark contrast to previous approaches, the formation dye is an inherent result chemical reaction and no additional fluorophores are needed in reagents. The crucial structural elements determine electron-donating groups present starting tetrazine unit. newly formed show interesting...
Cationic colloidal gold nanorods (GNRs) have a great potential as theranostic tool for diverse medical applications. GNRs' properties such cellular internalization and stability are determined by physicochemical characteristics of their surface coating. GNRs modified (16-mercaptohexadecyl)trimethylammonium bromide (MTAB), MTABGNRs, show excellent uptake. Despite promise biomedicine, however, relatively little is known about the pathways that facilitate uptake GNRs, subcellular fate...
Abstract Plasma membrane tension is an important feature that determines the cell shape and influences processes such as motility, spreading, endocytosis exocytosis. Unconventional class 1 myosins are potent regulators of plasma because they physically link with adjacent cytoskeleton. We identified nuclear myosin (NM1) - a putative isoform 1c (Myo1c) new player in field. Although having specific functions, NM1 localizes predominantly to membrane. Deletion causes more than 50% increase...
The development of abiotic chemical reactions that can be performed in an organelle-specific manner provide new opportunities drug delivery and cell biology. However, due to the complexity cellular environment, this remains a significant challenge. Here, we introduce structurally redesigned bioorthogonal tetrazine reagents spontaneously accumulate mitochondria live mammalian cells. attributes leading their efficient accumulation organelle were optimized include right combination...
Fluorogenic probes, which become fluorescent only upon specific activation, enable no-wash imaging with an excel-lent signal-to-noise ratio. Despite significant progress in the development of such challenges remain achiev-ing efficient quenching and substantial fluorescence enhancement across whole visible spectrum while maintain-ing good synthetic accessibility. In this work, we introduce a new class bioorthogonally activatable fluorogenic probes based on triazinium salts (Trz+), act as...
Fluorogenic probes, which become fluorescent only upon specific activation, enable no-wash imaging with an excel-lent signal-to-noise ratio. Despite significant progress in the development of such challenges remain achiev-ing efficient quenching and substantial fluorescence enhancement across whole visible spectrum while maintain-ing good synthetic accessibility. In this work, we introduce a new class bioorthogonally activatable fluorogenic probes based on triazinium salts (Trz+), act as...
Fluorogenic bioorthogonal reactions enable visualization of biomolecules under native conditions with excellent signal-to-noise ratio. Here, we present the design and synthesis conformationally-strained aziridine-fused trans-cyclooctene (aza-TCO) dienophiles, which lead to formation fluorescent products in tetrazine ligations without need for attachment an extra fluorophore moiety. The presented aza-TCOs adopt highly strained "half-chair" conformation, was predicted computationally confirmed...
Abstract Inverse‐electron‐demand Diels–Alder (iEDDA) cycloaddition between 1,2,4,5‐tetrazines and strained dienophiles belongs among the most popular bioconjugation reactions. In addition to its fast kinetics, this can be tailored produce fluorescent products from non‐fluorescent starting materials. Here we show that even reaction intermediates formed in iEDDA lead formation of new types fluorophores. The influence various substituents on their photophysical properties generality approach...
Paxillin (PXN) is a focal adhesion protein implicated in signal transduction from the extracellular matrix. Recently, it has been shown to shuttle between cytoplasm and nucleus. When inside nucleus, paxillin promotes cell proliferation. Here, we introduce as transcriptional regulator of IGF2 H19 genes. It does not affect allelic expression two genes; rather, regulates long-range chromosomal interactions or promoter shared distal enhacer on an active allele. Specifically, stimulates...
Aging involves tissue accumulation of senescent cells (SC) whose elimination through senolytic approaches may evoke organismal rejuvenation. SC also contribute to aging-associated pathologies including cancer, hence it is imperative better identify and target SC. Here, we aimed new cell-surface proteins differentially expressed on human Besides previously reported enriched SC, identified 78 73 underrepresented in replicatively BJ fibroblasts, L1CAM, expression normally restricted the neural...
Abstract The development of fluorogenic reactions which lead to the formation fluorescent products from two nonfluorescent starting materials is highly desirable, but challenging. Reported herein a new concept product upon inverse electron‐demand Diels–Alder reaction 1,2,4,5‐tetrazines with particular trans ‐cyclooctene (TCO) isomers. In sharp contrast known reagents presented chemistry leads rapid unprecedented 1,4‐dihydropyridazines so that fluorophore built directly chemical reaction....
Bioorthogonal bond‐cleavage reactions have emerged as a powerful tool for precise spatiotemporal control of (bio)molecular function in the biological context. Among these chemistries, tetrazine‐triggered elimination cleavable trans‐cyclooctenes (click‐to‐release) stands out due to high reaction rates, versatility, and selectivity. Despite an increasing understanding underlying mechanisms, application this remains limited by cumulative performance trade‐offs (i.e., click kinetics, release...
Abstract Bioorthogonal cleavage reactions are gaining popularity in chemically inducible prodrug activation and the control of biomolecular functions. Despite similar applications, these were developed optimized on different substrates under experimental conditions. Reported herein is a side‐by‐side comparison palladium‐, ruthenium‐ tetrazine‐triggered release reactions, which aims at comparing reaction kinetics, efficiency overall advantages limitations methods. In addition, we disclose...
Radiation and chemotherapy represent standard‐of‐care cancer treatments. However, most patients eventually experience tumour recurrence, treatment failure metastatic dissemination with fatal consequences. To elucidate the molecular mechanisms of resistance to radio‐ chemotherapy, we exposed human cell lines (HeLa, MCF‐7 DU 145) clinically relevant doses 5‐azacytidine or ionizing radiation compared transcript profiles all surviving subpopulations, including low‐adherent stem‐like cells....