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Papers by Alexander Slita

Russian Journal of Applied Chemistry, 2005

Water-soluble methanofullerene and fulleropyrrolidine derivatives were synthesized by the reactio... more Water-soluble methanofullerene and fulleropyrrolidine derivatives were synthesized by the reactions of methanofullerenes (MFs) and fulleropyrrolidines (FPs) with poly(N-vinylpyrrolidone) (PVP) bearing one terminal amino group. The products contain MF or FP covalently bound to the polymer, corresponding polymeric complexes, and unreacted PVP. Large aggregates of the polymeric MF and FP derivatives are found in aqueous solutions. The electrooptical properties of the products differ considerably from those of the initial polymer. The phosphorus-containing MF and FP derivatives are capable of cleaving the molecule of plasmid DNA.

Journal of Carbohydrate Chemistry, 2009

New copolymers of the vinyl saccharide 2 deoxy 2 methacrylamido D glucose (M 1 ) with acrylic and... more New copolymers of the vinyl saccharide 2 deoxy 2 methacrylamido D glucose (M 1 ) with acrylic and methacrylic (M 2 ) acids differing in composition and molecular mass have been synthesized by free rad ical copolymerization. The relative activities of the comonomers are determined. It is found that, for acrylic acid, r 1 = 3.03 ± 0.15 and r 2 = 0.5 ± 0.08 and, for methacrylic acid, r 1 = 1.070 ± 0.1 and r 2 = 1.18 ± 0.13. As is evidenced by potentiometric and viscometric measurements, the vinyl saccharide and acid units are capable of interacting, a circumstance that affects the conformational states of macromolecules.

Russian Journal of General Chemistry, 2008

Low molecular weight chitosans (5 kDa) hydrophobically modified with 3, 10, and 18 mol % of tetra... more Low molecular weight chitosans (5 kDa) hydrophobically modified with 3, 10, and 18 mol % of tetradecenoyl (TDC) groups have been synthesized. Their good solubility at neutral pH, their surface activity and micelle-forming properties as well as their ability to interact with negatively charged phospholipid vesicles mimicking the internal layer of cell plasma membranes, allow us to consider them as potential non-viral transfection vectors for gene therapy.

Antiviral Research, 2003

Adenoviruses represent a broad group of human pathogens that currently have no specific and safe ... more Adenoviruses represent a broad group of human pathogens that currently have no specific and safe drugs for treatment. We demonstrated direct (non IFN-mediated) antiviral activity of cycloferon (10-carboxymethyl-9-acridanone, CMA), a potent interferon inducer, against adenovirus type 6 (Ad6) in Hep-2 cells. Virus production and details of morphogenesis were studied by ELISA with antibodies to the Ad6 hexon protein, and transmission electron microscopy, respectively. Immunoenzyme assay revealed that CMA does not inhibit viral protein synthesis but instead strongly reduces the ability of the virus to generate infectious progeny virus in a dose dependent manner. Ultrastructural study shows that CMA alters the structure of intranuclear virus-specific inclusions. We suggest that CMA suppresses the late stages of viral cycle in the infected cell.

Biophysics, 2008

Generation and physicochemical properties of complexes formed by high-molecular thymus DNA and pl... more Generation and physicochemical properties of complexes formed by high-molecular thymus DNA and plasmid DNA with synthetic polymers of (dimethyl amino)ethyl methacrylate, (diethyl amino)ethyl methacrylate, and poly(vinyl amine) were studied in solutions of different ionic strength using low-gradient viscometry, electrophoresis, circular dichroism, spectrophotometry, and dynamic light scattering. The complexes were tested for toxicity with T98G cell cultures. Condensation of DNA was shown to occur when the ratio of charged groups in the polycations and DNA exceeded unity. This condensation manifested itself as an increase in the optical density of DNA solutions. Condensation-associated changes in the dimensions of DNA molecules were determined, and phase diagrams of DNA-polycation systems were analyzed in the presence of NaCl. MTT analysis revealed no toxicity of these complexes.

Russian Journal of Applied Chemistry, 2007

Nontoxic water-soluble low-molecular-weight (MW 14 000–36 000 Da) copolymers of acrylamide with 2... more Nontoxic water-soluble low-molecular-weight (MW 14 000–36 000 Da) copolymers of acrylamide with 2-acrylamido-2-methylpropanesulfonic acid, containing from 17.3 to 37.6 mol % sulfonate-containing monomeric units, were synthesized by heterophase radical polymerization in isopropanol or ethanol at 50°C with azobis(isobutyronitrile) as an initiator.

Journal of Biotechnology, 2007

The purpose of the study was to investigate the influence of cationic polymer structure on the fo... more The purpose of the study was to investigate the influence of cationic polymer structure on the formation of DNA-polycation complexes and their transfection activity. Primary, tertiary, and quaternary polyamines with molecular masses ranging from 8000 to 200,000 were investigated. DNA-cationic polymer interaction was characterized by low gradient viscometry, dynamic light scattering, circular dichroism, UV spectrometry, flow birefringence, DNA electrophoresis, and electron microscopy. Transfection activity of the complexes was evaluated by the expression of reporter gene (␤-galactosidase) and using synthetic FITC-labelled oligonucleotides. Complex formation was found to be dependent on the structure and molecular weight of the polymer and the ionic strength of the solution. Secondary DNA structure in complexes was not disrupted, and DNA was protected from protonation. Cell lines of different origin were used for testing of transfection activity of the complexes. The sensitivity of the cells to transfection was established to be highly dependent on the cell line. DNA-polycation complexes are non-toxic according to MTT. Polyallylamine, and polydimethylaminoethylmethacrylate were found to be the most promising polycations for gene delivery. Transfection efficacy of their complexes with DNA to T-98G cells reaches up to 90-100%. It was found that optimal molecular mass of polydimethylaminoethylmethacrylate is in the range of 8000-50,000 Da.

Viruses are the most dangerous contaminants of human blood and blood products. The purpose of thi... more Viruses are the most dangerous contaminants of human blood and blood products. The purpose of this study was to investigate the light-mediated virus-inactivating properties of fullerene and its effect on the intactness of biological fluids. Influenza virus was propagated in chicken embryos, and a water suspension of C60 fullerene was added to the allantoic fluid. The fluid was light-irradiated with a constant flow of oxygen through the specimen, and the dynamics of the virus titer were studied in Madin-Darby canine kidney (MDCK) cells. The morphology of the virions was studied by electron microscopy (EM). The electrophoretic pattern of the proteins in the allantoic fluid and blood plasma, as well as the growth properties of the calf serum were compared before and after 6h of irradiation. A dramatic drop of infectious titer (from 6 to 0 log10 EID50) in the virus was observed within 2h after the start of irradiation. No change in the titers was observed in control specimens without the fullerene, or light, or oxygen. EM revealed numerous defects in the morphology of the virions (destruction of the outer membrane) leading to the loss of infectious properties in the virus. Based on comparison of proteins and growth properties of the serum, no differences were revealed between intact and irradiated biological fluids. Water-insoluble fullerenes may therefore be considered an effective and safe way to inactivate enveloped viruses in biological materials including blood products.

Journal of Gene Medicine, 2008

BackgroundChitosan derivatives are potential candidates for gene delivery because they are biocom... more BackgroundChitosan derivatives are potential candidates for gene delivery because they are biocompatible and low toxic. However, their use has been limited by their moderate transfection efficiency and the rather large sizes of DNA complexes with high molecular weight chitosans. To circumvent these limitations, we used low molecular weight (approximately 5 kDa) chitosans grafted at 3 and 18 mol% with N-/2(3)-(dodec-2-enyl)succinoyl groups (HM-LMW-ch) that exhibit surfactant-like properties.Chitosan derivatives are potential candidates for gene delivery because they are biocompatible and low toxic. However, their use has been limited by their moderate transfection efficiency and the rather large sizes of DNA complexes with high molecular weight chitosans. To circumvent these limitations, we used low molecular weight (approximately 5 kDa) chitosans grafted at 3 and 18 mol% with N-/2(3)-(dodec-2-enyl)succinoyl groups (HM-LMW-ch) that exhibit surfactant-like properties.MethodsThe physico-chemical properties of complexes of DNA with the two HM-LMW-ch derivatives and the nonmodified LMW-ch were compared by electrophoresis, dynamic light scattering, fluorescence spectroscopy and fluorescence correlation spectroscopy. Moreover, their transfection efficiencies and cytotoxicity were evaluated and their intracellular trafficking was monitored by confocal microscopy. Finally, their ability to deliver genes in mice kidneys after systemic administration was investigated.The physico-chemical properties of complexes of DNA with the two HM-LMW-ch derivatives and the nonmodified LMW-ch were compared by electrophoresis, dynamic light scattering, fluorescence spectroscopy and fluorescence correlation spectroscopy. Moreover, their transfection efficiencies and cytotoxicity were evaluated and their intracellular trafficking was monitored by confocal microscopy. Finally, their ability to deliver genes in mice kidneys after systemic administration was investigated.ResultsComplexes with HM(3%)-LMW-ch, but not with HM(18%)-LMW-ch and LMW-ch, efficiently delivered genes in mice kidneys. HM(3%)-LMW-ch formed small positively charged particles that were resistant to DNases and nucleases and marginally interact with serum components. Moreover, these particles were efficiently internalized in cells and low toxic. By contrast, HM(18%)-LMW-ch formed large and weakly charged aggregates with DNA that were highly susceptible to DNases and nucleases.Complexes with HM(3%)-LMW-ch, but not with HM(18%)-LMW-ch and LMW-ch, efficiently delivered genes in mice kidneys. HM(3%)-LMW-ch formed small positively charged particles that were resistant to DNases and nucleases and marginally interact with serum components. Moreover, these particles were efficiently internalized in cells and low toxic. By contrast, HM(18%)-LMW-ch formed large and weakly charged aggregates with DNA that were highly susceptible to DNases and nucleases.ConclusionsHM(3%)-LMW-ch appears to be a promising nonviral vector with low cytotoxicity and efficient transfection properties. Copyright © 2008 John Wiley & Sons, Ltd.HM(3%)-LMW-ch appears to be a promising nonviral vector with low cytotoxicity and efficient transfection properties. Copyright © 2008 John Wiley & Sons, Ltd.