A5015691615- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Synthesis and Reactions of Organic Compounds
- Synthesis and Biological Evaluation
- Synthesis and Characterization of Heterocyclic Compounds
- Synthesis and biological activity
- Computational Drug Discovery Methods
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Crystallography and molecular interactions
- Ion channel regulation and function
- Cancer, Hypoxia, and Metabolism
- HIV/AIDS drug development and treatment
- Protein Structure and Dynamics
- Chemical Reactions and Isotopes
- Protein Tyrosine Phosphatases
- DNA and Nucleic Acid Chemistry
- Synthesis and Reactivity of Heterocycles
- Bacteriophages and microbial interactions
- Neuroscience and Neuropharmacology Research
- Enzyme Structure and Function
- Hippo pathway signaling and YAP/TAZ
- Fluorine in Organic Chemistry
- Cancer-related Molecular Pathways
- Cytokine Signaling Pathways and Interactions
Enamine (Ukraine)
2013-2024
Institute of Molecular Biology and Genetics
2012-2024
National Academy of Sciences of Ukraine
2005-2024
Taras Shevchenko National University of Kyiv
2001-2021
N.D. Zelinsky Institute of Organic Chemistry
2006
The filovirus Ebola (EBOV) causes the most severe hemorrhagic fever known. EBOV RNA-dependent polymerase complex includes a filovirus-specific VP30, which is critical for transcriptional but not replication activity of polymerase; to support transcription, VP30 must be in dephosphorylated form. Here we show that phosphorylated only at N-terminal serine clusters identified previously also threonine residues positions 143 and 146. We host cell protein phosphatase 1 (PP1) controls...
Designing a sturdy label: The fluorinated amino acid l-CF3-Bpg (see picture), which was specifically designed as 19F NMR label for structure analysis of membrane-bound peptides, does not display the drawbacks previously used labels. can be readily incorporated into peptides and is particularly suitable substitute Leu, Ile, Met.
Abstract A conformationally restricted monofluorinated α‐amino acid, (3‐fluorobicyclo[1.1.1]pentyl)glycine (F‐Bpg), was designed as a label for the structural analysis of membrane‐bound peptides by solid‐state 19 F NMR spectroscopy. The compound synthesized and validated replacing natural aliphatic acids. Calculations suggested that F‐Bpg is similar to Leu/Ile in terms size lipophilicity. incorporated into membrane‐active antimicrobial peptide PGLa provided information on structure lipid bilayer.
Abstract Exosomes support cell‐to‐cell communication in physiology and disease, including cancer. We currently lack tools, such as small chemicals, capable of modifying exosome composition activity a specific manner. Building on our previous understanding how syntenin, its PDZ partner syndecan (SDC), impact we optimized chemical compound targeting the PDZ2 domain syntenin. In vitro , tests MCF‐7 breast carcinoma cells, this is non‐toxic impairs cell proliferation, migration primary sphere...
HIV-1 Tat protein recruits host cell factors including CDK9/cyclin T1 to TAR RNA and thereby induces transcription. An interaction with Ser/Thr phosphatase-1 (PP1) is critical for this function of Tat. PP1 binds a sequence, Q35VCF38, which resembles the PP1-binding "RVxF" motif present on regulatory subunits. We showed that expression binding peptide, central domain Nuclear Inhibitor PP1, disrupted inhibited transcription replication. Here, we report small molecule compounds target...
HIV-1 transcription is activated by the Tat protein which recruits cyclin-dependent kinase CDK9/cyclin T1 to TAR RNA. binds phosphatase-1 (PP1) through Q(35) VCF(38) sequence and translocates PP1 nucleus. dephosphorylates CDK9 activates transcription. We have synthesized a low MW compound 1H4, that targets prevents interaction with inhibits gene Here, we report our further work 1H4-derived compounds analysis of their mechanism action.Using 1H4-PP1 complex as model, iteratively designed...
Photoisomerization of diarylethene-modified peptides changes the thermodynamics their binding to MDM2: “closed” photoisomers bind largely due a high negative enthalpy, whereas “open” forms better more favourable entropy.
Eine robuste Markierung: Die fluorierte Aminosäure l-CF3-Bpg (siehe Bild), die gezielt als 19F-NMR-Markierung für Strukturanalyse an membrangebundenen Peptiden konzipiert wurde, ist frei von den Nachteilen früher verwendeter Markierungen. lässt sich einfach in Peptide einbauen und eignet besonders Ersatz Leu, Ile Met.
An approach to the parallel synthesis of hydantoin libraries by reaction in situ generated 2,2,2-trifluoroethylcarbamates and α-amino esters was developed. To demonstrate utility method, a library 1158 hydantoins designed according lead-likeness criteria (MW 200-350, cLogP 1-3) prepared. The success rate method analyzed as function physicochemical parameters products, it found that can be considered tool for lead-oriented synthesis. A hydantoin-bearing submicromolar primary hit acting an...
Abstract A new oxidation process has been found where α,ω-dicarboxylic acid esters and ω-hydroxycarboxylic are formed on heating gem-bishydroperoxides in alcohol the presence of BF3·Et2O. By addition H2O2 to this reaction almost selectively.
Multigram synthesis of (chlorosulfonyl)benzenesulfonyl fluorides is described. Selective modification these building blocks at the sulfonyl chloride function under parallel conditions achieved. It shown that reaction scope includes use (hetero)aromatic and electron-poor aliphatic amines (e.g., amino nitriles). Utility method demonstrated by preparation fluoride library for potential as covalent fragments, which a combination in silico vitro screening against trypsin model enzyme. As result,...
A conformationally restricted monofluorinated α-amino acid, (3-fluorobicyclo[1.1.1]pentyl)glycine (F-Bpg), was designed as a label for the structural analysis of membrane-bound peptides by solid-state 19F NMR spectroscopy. The compound synthesized and validated replacing natural aliphatic acids. Calculations suggested that F-Bpg is similar to Leu/Ile in terms size lipophilicity. incorporated into membrane-active antimicrobial peptide PGLa provided information on structure lipid bilayer.
Acid-sensing ion channels (ASICs) play a key role in the perception and response to extracellular acidification changes. These proton-gated cation are critical for neuronal functions, like learning memory, fear, mechanosensation internal adjustments synaptic plasticity. Moreover, they degeneration, ischemic injury, seizure termination, pain-sensing, etc. Functional ASICs homo or heterotrimers formed with (ASIC1–ASIC3) homologous subunits. ASIC1a, major ASIC isoform central nervous system...
UDC 577.152.3 + 615.32 Антивірусні влас ти вості рос лин них фла во ноїдівінгібіторів син те зу ДНК і РНК Л. Г. Паль чи ко вська 1 , О. В. Ва силь чен М. Пла то нов Д. Б. Ста ро си ла 2 Ю. І. Пор ва С. Ри мар П. Атаманюк Самійлен бал Інсти тут мо ле ку ляр ної біології ге не ки НАН Украї ни Вул.Академіка За бо лот но го
Keywords: 1,2,4-triazino[5,6-b][1,4]benzothiazines, design, virtual screening, synthesis, model transcription system
Keywords: N-arylamides 9-substituted PCA, model system of the DNA-dependent RNA-polymerase phage T7, antibacterial activity, antiviral activity
Molecular docking is a widely used method of computer-aided drug design capable accurate prediction protein-ligand complex conformations.However, scoring functions to estimate free energy binding still lack accuracy.Aim.Development computationally simple and rapid algorithms for ranking ligands based on results.Methods.Computational filters utilizing geometry were designed.Efficiency the was verified in cross-docking study with QXP/Flo software using crystal structures human serine proteases...
Dishevelled (Dvl) proteins are important regulators of the Wnt signalling pathway, interacting through their PDZ domains with receptor Frizzled. Blocking Dvl PDZ-Frizzled interaction represents a potential approach for cancer treatment, which stimulated identification small-molecule inhibitors, among them anti-inflammatory drug Sulindac and Ky-02327. Aiming to develop tighter binding compounds without side effects, we investigated structure-activity relationships sulfonamides. X-ray...