Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests: Chemistry, Biology, Calcium, Medicine, Environmental Biotechnology, and 13 moreProtein Stability, Magnesium, Staphylococcus aureus, Enzyme, Reproducibility of Results, Species Specificity, Microbial enzyme Technology, Bacteriophage, Hydrogen-Ion Concentration, Sodium Chloride, Lysis, Lytic Cycle, and drug storage
Research Interests:
Complexes of hen egg white lysozyme (HEWL) with alginate (ALG) and chitosan (CS) (natural biodegradable polysaccharides) are important as antimicrobial agents in oral, intranasal and buccal administration. The HEWL–ALG, HEWL–ALG–Ca,... more
Complexes of hen egg white lysozyme (HEWL) with alginate (ALG) and chitosan (CS) (natural biodegradable polysaccharides) are important as antimicrobial agents in oral, intranasal and buccal administration. The HEWL–ALG, HEWL–ALG–Ca, [HEWL–ALG]–CS, and [HEWL–ALG–Ca]–CS complexes have been investigated using a combination of physicochemical methods (fluorescent spectroscopy, circular dichroism, microscopy, turbidimetry, microbiology, <i>in vitro</i> cytotoxicity assay). The complexes obtained were non-toxic negatively charged microparticles with high HEWL entrapment efficiency. The [HEWL–ALG]–CS and [HEWL–ALG–Ca]–CS complexes were found to have the altered tertiary structure of HEWL (and/or changes in the polarity of the microenvironment of Trp residues in HEWL molecules). The HEWL entrapment in all studied complexes was carried out with retention of the HEWL activity. Under the long–term storage conditions (1.5 years at 4 °C), Ca<sup>++</sup> cations and CS stabilized HEWL. Under physiological conditions, the [HEWL–ALG]–CS and [HEWL–ALG–Ca]–CS complexes demonstrated sustained release of HEWL and resistance to protease action. The [HEWL–ALG]–CS and [HEWL–ALG–Ca]–CS complexes were highly active against Gram-negative <i>Escherichia coli</i> cells. The data obtained are important in the development of antibacterial drugs based on lytic enzymes.
Research Interests:
Research Interests:
Research Interests:
... Natalia L. Klyachko and Andrey V. Levashov ... 70. Rariy, RV; Klyachko, NL; Borisova, EA; Cortes -Penagos, CJ; Levashov, AV Lectin-like center in the molecule of a-chymotrypsin: formation of complexes with peroxidase and artificially... more
... Natalia L. Klyachko and Andrey V. Levashov ... 70. Rariy, RV; Klyachko, NL; Borisova, EA; Cortes -Penagos, CJ; Levashov, AV Lectin-like center in the molecule of a-chymotrypsin: formation of complexes with peroxidase and artificially glycosylated a-chymotrypsin. Biochem. Mol. ...
Research Interests:
Research Interests:
ABSTRACT The dynamics of single-domain magnetic nanoparticles cross-linked into multiparticle aggregates by organic ligands is considered. Mechanical factors of the effect of low frequency magnetic field on macromolecules attached to... more
ABSTRACT The dynamics of single-domain magnetic nanoparticles cross-linked into multiparticle aggregates by organic ligands is considered. Mechanical factors of the effect of low frequency magnetic field on macromolecules attached to magnetic nanoparticles/aggregates within a suspension or gel are analyzed. The optimum conditions ensuring the best control over biochemical reactions in suspension by an external magnetic field (i.e., the ranges of frequency and magnetic field intensities, and the size of magnetic nanoparticles and shells covering them) are determined.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Catalytic properties of α-chymotrypsin, peroxidase and laccase, dissolved in water-immiscible organic solvents by entrapping them into the reversed micelles of surfactants solvated by water/organic cosolvent (glycerol or 1,4- or... more
Catalytic properties of α-chymotrypsin, peroxidase and laccase, dissolved in water-immiscible organic solvents by entrapping them into the reversed micelles of surfactants solvated by water/organic cosolvent (glycerol or 1,4- or 2,3-butanediol or dimethyl sulfoxide) mixtures, are studied. As micelle-forming surfactants, sodium salt of bis(2-ethylhexyl)sulfosuccinate (Aerosol OT) in n-octane or cetyltrimethylammonium bromide in n-octane/chloroform (1 : 1 by volume) mixture are used. The dependences of the catalytic activity on the surfactant solvation degree are bell-shaped. Maxima of the catalytic activity of enzymes solubilized in the micellar systems are observed at such optimum values of the surfactant solvation degree at which the size of micellar inner cavity and of the entrapped protein molecule is approximately equal. With decreasing content of water in the micellar media studied, the catalytic activity of the solubilized enzymes increases considerably, and is much (10-100 times) higher than in bulk aqueous buffers. In conclusion, possible mechanisms of the micellar effects are suggested.
Research Interests:
Research Interests:
Research Interests:
Formulations on the base of an inhibitor of angiotensin-converting enzyme, enalaprilat, were prepared by the inclusion of the drug into calcium phosphate (CaP)-particles in situ, followed by the covering of the particles with 5 kDa... more
Formulations on the base of an inhibitor of angiotensin-converting enzyme, enalaprilat, were prepared by the inclusion of the drug into calcium phosphate (CaP)-particles in situ, followed by the covering of the particles with 5 kDa chitosan or 72 kDa glycol chitosan and cross-linking with sodium tripolyphosphate. Physicochemical characterization of the resulted hybrid particles was conducted using dynamic light scattering, as well as scanning and transmission electron microscopy. Enalaprilat-containing particles had a mean hydrodynamic diameter 180 nm and 260 nm and ζ-potential +7 mV and +16 mV for 5 kDa and 72 kDa chitosans, respectively. In vivo studies showed that enalaprilat within particles stayed longer in the tear fluid after single instillation and caused a significantly pronounced and prolonged decrease of intraocular pressure in rabbits, especially in the case of CaP-particles, covered by glycol chitosan. Thus, such formulations demonstrate potential as prospective therapeutic agents for the treatment of eye diseases.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests: Chemistry, Organic Chemistry, Quantum Theory, Medicine, Antioxidants, and 15 moreHumans, Copper, Combinatorial Chemistry, Glutathione Peroxidase, Organoselenium Compounds, Ebselen, Pyridines, Isomerization, Bioorganic and medicinal Chemistry, Molecule, Cell Survival, Antineoplastic Agents, Pharmacology and pharmaceutical sciences, Azoles, and Minimum Inhibitory Concentration
Research Interests:
Research Interests:
Research Interests:
Research Interests:
In this work, the effect of the new synthesized anticancer conjugates on the HepG2 and PC-3 cell lines was evaluated by determining ROS inside single cells using an electrochemical method.
Research Interests:
The conjugates of paclitaxel and betulin with N-acetylgalactosamine were obtained, their affinity to the asialoglycoprotein receptor was evaluated via surface plasmon resonance spectroscopy technique. Thermodynamic dissociation constants... more
The conjugates of paclitaxel and betulin with N-acetylgalactosamine were obtained, their affinity to the asialoglycoprotein receptor was evaluated via surface plasmon resonance spectroscopy technique. Thermodynamic dissociation constants (KD) were determined. The influence of the structural elements of the linker on the binding of the receptor was studied.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Macrophages are desirable targets for gene therapy of cancer and other diseases. Cationic diblock copolymers of polyethylene glycol (PEG) and poly-L-lysine (PLL) or poly{N-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} (pAsp(DET)) are... more
Macrophages are desirable targets for gene therapy of cancer and other diseases. Cationic diblock copolymers of polyethylene glycol (PEG) and poly-L-lysine (PLL) or poly{N-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} (pAsp(DET)) are synthesized and used to form polyplexes with a plasmid DNA (pDNA) that are decorated with mannose moieties, serving as the targeting ligands for the C type lectin receptors displayed at the surface of macrophages. The PEG-b-PLL copolymers are known for its cytotoxicity, so PEG-b-PLL-based polyplexes are cross-linked using reducible reagent dithiobis(succinimidyl propionate) (DSP). The cross-linked polyplexes display low toxicity to both mouse embryonic fibroblasts NIH/3T3 cell line and mouse bone marrow-derived macrophages (BMMΦ). In macrophages mannose-decorated polyplexes demonstrate an ≈8 times higher transfection efficiency. The cross-linking of the polyplexes decrease the toxicity, but the transfection enhancement is moderate. The PEG-b-pAsp(DET) copolymers display low toxicity with respect to the IC-21 murine macrophage cell line and are used for the production of non-cross-linked pDNA-contained polyplexes. The obtained mannose modified polyplexes exhibit ca. 500-times greater transfection activity in IC-21 macrophages compared to the mannose-free polyplexes. This result greatly exceeds the targeting gene transfer effects previously described using mannose receptor targeted non-viral gene delivery systems. These results suggest that Man-PEG-b-pAsp(DET)/pDNA polyplex is a potential vector for immune cells-based gene therapy.
Research Interests:
Research Interests:
Atorvastatin conjugates targeting the galactose-specific hepatic asialoglycoprotein receptor with improved stability are reported.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Herein, we describe the design, synthesis, and biological evaluation of novel betulin and N-acetyl-d-galactosamine (GalNAc) glycoconjugates and suggest them as targeted agents against hepatocellular carcinoma. We prepared six conjugates... more
Herein, we describe the design, synthesis, and biological evaluation of novel betulin and N-acetyl-d-galactosamine (GalNAc) glycoconjugates and suggest them as targeted agents against hepatocellular carcinoma. We prepared six conjugates derived via the C-3 and C-28 positions of betulin with one or two saccharide ligands. These molecules demonstrate high affinity to the asialoglycoprotein receptor (ASGPR) of hepatocytes assessed by in silico modeling and surface plasmon resonance tests. Cytotoxicity studies in vitro revealed a bivalent conjugate with moderate activity, selectivity of action, and cytostatic properties against hepatocellular carcinoma cells HepG2. An additional investigation confirmed the specific engagement with HepG2 cells by the enhanced generation of reactive oxygen species. Stability tests demonstrated its lability to acidic media and to intracellular enzymes. Therefore, the selected bivalent conjugate represents a new potential agent targeted against hepatocellular carcinoma. Further extensive studies of the cellular uptake in vitro and the real-time microdistribution in the murine liver in vivo for fluorescent dye-labeled analogue showed its selective internalization into hepatocytes due to the presence of GalNAc ligand in comparison with reference compounds. The betulin and GalNAc glycoconjugates can therefore be considered as a new strategy for developing therapeutic agents based on natural triterpenoids.