A5020732741- DNA Repair Mechanisms
- Plant Genetic and Mutation Studies
- DNA and Nucleic Acid Chemistry
- HIV Research and Treatment
- Carcinogens and Genotoxicity Assessment
- HIV/AIDS drug development and treatment
- RNA Interference and Gene Delivery
- Galectins and Cancer Biology
- Chemical Synthesis and Analysis
- Photochromic and Fluorescence Chemistry
- Advanced Fluorescence Microscopy Techniques
- Mosquito-borne diseases and control
- Advanced biosensing and bioanalysis techniques
- Signaling Pathways in Disease
- Biochemical and Molecular Research
- Education, Psychology, and Social Research
- Plant tissue culture and regeneration
- Immune Response and Inflammation
- Soft tissue tumor case studies
- Peptidase Inhibition and Analysis
- Diet and metabolism studies
- Metabolism and Genetic Disorders
- Thermal Regulation in Medicine
- thermodynamics and calorimetric analyses
- Folate and B Vitamins Research
Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry
2013-2025
Charles University
1958-2022
General University Hospital in Prague
2022
University of Cambridge
2022
Czech Academy of Sciences, Institute of Experimental Botany
2009-2014
University of Leeds
2011
Slovak Academy of Sciences
1996
Czech Academy of Sciences, Institute of Physiology
1958-1966
DNA ligase enzymes catalyse the joining of adjacent polynucleotides and as such play important roles in replication repair pathways. Eukaryotes possess multiple ligases with distinct metabolism, clear differences functions orthologues between animals, yeast plants. 1, present all eukaryotes, plays critical both is indispensable for cell viability. Knockout mutants atlig1 are lethal. Therefore, RNAi lines reduced levels AtLIG1 were generated to allow importance Arabidopsis 1 metabolism be...
A series of 7-deazaadenine ribonucleosides bearing alkyl, alkenyl, alkynyl, aryl, or hetaryl groups at position 7 as well their 5'-O-triphosphates and two types monophosphate prodrugs (phosphoramidates S-acylthioethanol esters) were prepared tested for antiviral activity against selected RNA viruses (Dengue, Zika, tick-borne encephalitis, West Nile, SARS-CoV-2). The modified triphosphates inhibited the viral RNA-dependent polymerases micromolar concentrations through incorporation nucleotide...
The moss Physcomitrella patens is unique among plant models for the high frequency with which targeted transgene insertion occurs via homologous recombination. Transgene integration believed to utilize existing machinery detection and repair of DNA double-strand breaks (DSBs). We undertook knockout genes encoding components principal sensor DSBs, MRN complex. Loss function PpMRE11 or PpRAD50 strongly specifically inhibited gene targeting, whilst rates untargeted were relatively unaffected....
The search for new drugs against COVID-19 and its causative agent, SARS-CoV-2, is one of the major trends in current medicinal chemistry. Targeting capping machinery could be therapeutic concepts based on a unique mechanism action. Viral RNA cap synthesis involves two methylation steps, first which mediated by nsp14 protein. Here, we rationally designed synthesized series compounds capable binding to both S-adenosyl-l-methionine RNA-binding site SARS-CoV-2 N7-methyltransferase. These hybrid...
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...
The cation‐independent mannose‐6‐phosphate/IGF2 receptor (CI‐M6P/IGF2R) plays a crucial role in transporting lysosomal enzymes and other ligands. In this study, we designed synthesized novel, stable mannose‐6‐phosphate (M6P) derivatives to enhance their affinity for CI‐M6P/IGF2R. To evaluate binding potency, employed sensitive cost‐effective fluorescence polarization assay, enabling rapid quantification of receptor‐ligand interactions solution. tested compounds included di‐, tri‐, penta‐M6P...
DNA double-strand breaks (DSBs) pose one of the most severe threats to genome integrity, potentially leading cell death. After detection a DSB, damage and repair response is initiated DSB repaired by non-homologous end joining and/or homologous recombination. Many components these processes are still unknown in Arabidopsis thaliana. In this work, we characterized γ-irradiation mitomycin C induced 1 (GMI1), member SMC-hinge domain-containing protein family. RT-PCR analysis promoter-GUS fusion...
The RAD21 cohesin plays, besides its well-recognised role in chromatid cohesion, a DNA double strand break (dsb) repair. In Arabidopsis there are three paralog genes (AtRAD21.1, AtRAD21.2 and AtRAD21.3), yet only AtRAD21.1 has been shown to be required for dsb damage Further investigation of the cohesins repair was carried out is here reported.We show first time that not but also AtRAD21.3 play somatic Comet data shows lack either induces similar high basal level nuclei slower kinetics both...
The moss Physcomitrella patens is unique for the high frequency of homologous recombination, haploid state, and filamentous growth during early stages vegetative growth, which makes it an excellent model plant to study DNA damage responses. We used single cell gel electrophoresis (comet) assay determine kinetics response Bleomycin induced oxidative double strand breaks in wild type mutant lig4 lines. Moreover, APT gene when inactivated by mutations was as selectable marker ascertain...
Yohimbine, a natural indole alkaloid and nonselective adrenoceptor antagonist, possesses potential benefits in treating inflammatory disorders sepsis. Nevertheless, its broader clinical use faces challenges due to low receptor selectivity. A structure-activity relationship study of novel yohimbine analogues identified amino esters yohimbic acid as potent selective ADRA2A antagonists. Specifically, ester
This work presents a novel series of galectin inhibitors with ferrocene and ruthenium arene motifs. Diferrocene thiodigalactoside exhibited high binding affinity selectivity for human galectin-1 over galectin-3.
Event Abstract Back to DNA repair in plants studied by comet assay Karel J. Angelis1*, Jaroslav Kozák2, Radka Vágnerová1 and Marcela Holá1 1 Institute of Experimental Botany AS CR, Czechia 2 Organic Chemistry Biochemistry Comet plants. From the first description with isolated nuclei rather than whole cells it became evident that is well suited be applied (Koppen & Verschaeve, 1996). Disintegration tissue quick chopping a razor blade, direct collection released patting pipetting enables...
Purine nucleoside phosphorylase (PNP) is a well-known molecular target with potential therapeutic applications in the treatment of T-cell malignancies and/or bacterial/parasitic infections. Here, we report design, development synthetic methodology, and biological evaluation series 30 novel PNP inhibitors based on acyclic phosphonates bearing 9-deazahypoxanthine nucleobase. The strongest exhibited IC50 values as low 19 nM (human PNP) 4 (Mycobacterium tuberculosis (Mt) highly selective...
Abstract The formation of a G‐quadruplex motif in the promoter region c‐MYC protooncogene prevents its expression. Accordingly, stabilization by suitable ligand may be viable approach for anticancer therapy. In our study, we used 4‐(4‐methylpiperazin‐1‐yl)aniline molecule, previously identified as fragment library screen hit, template SAR‐guided design new small clickable fragments and subjected them to click reactions, including kinetic target‐guided synthesis presence forming...
Abstract The secondary structure of nucleic acids containing quartets guanines, termed G-quadruplexes, is known to regulate the transcription many genes. Several G-quadruplexes can be formed in HIV-1 long terminal repeat promoter region and their stabilization results inhibition replication. Here, we identified helquat-based compounds as a new class anti-HIV-1 inhibitors that inhibit replication at stage reverse provirus expression. Using Taq polymerase stop FRET melting assays, have...
Abstract Galectins are a family of galactoside‐binding proteins involved in various pathophysiological processes, which makes them attractive targets for drug discovery. The derivatization d ‐galactose at C3 and C1 positions has been shown to increase the affinity synthetic galectin antagonists. In this study, two small libraries derivatives have designed synthesized. first series development novel aromatic 3‐azolyl‐3‐deoxy‐ ‐galactopyranoses. second consisted epimeric analogs glyceryl β‐ S...