Luminescent polyelectrolytes with antiviral activity.

Radical polymerization was used to synthesize and characterize (co)polymers with sodium styrenesulfonate (NaSS), 4-methacryloylamidosalicylic acid (MASA), and N-vinylpyrrolidone, which have a low cytotoxicity and a high antiviral activity against the human respiratory syncytial virus. The interaction of copolymers with Tb3+ ions was studied. The complexes formed in dilute aqueous solutions at a concentration of MASA units c ⩽ 1 · 10-4 mol L-1 demonstrate a strong luminescence. The luminescence intensity is independent of copolymer composition, but increases when the NaSS units are substituted with uncharged N-vinylpyrrolidone units. The obtained Tb3+ polymer complexes are promising luminescent sensors for the visualization of biological objects interacting with copolymers.

Synthesis and Anti-influenza Activity of Vinylphosphonic Acid (Co)polymers.

New copolymers of vinylphosphonic acid (VPA) with 2-deoxy-2-methacrylamido-D-glucose, 4-acryloylmorpholine (4-AM), and acrylamide have been synthesized, and their antiviral activity against influenza virus has been studied in in vitro and in vivo experiments. Optimal antiviral characteristics and low cytotoxicity were exhibited by the copolymer of VPA with 4-AM, composition 56 : 44 mol %, molecular weight 33 000. The polymer exhibited virus-inhibiting properties with an IC50 = 1 µg/mL and a selectivity index of 302. Prophylactic intranasal administration of the polymer in a murine model of influenza pneumonia completely prevented the virus-induced death of animals, whereas the level of mortality in the placebo group was 90%. The results of this study indicate a high antiviral potential of polymeric compounds based on VPA.

Biologically active polymer nanosystems.

The methods of synthesis of biologically active nanostructured systems based on functional and natural polymers are reviewed. The formation of nanosystems in the process of interaction between synthetic water-soluble polyelectrolytes and amphiphilic ionic surfactants is discussed. The influence of structure and stability of these systems on their biological activity is considered. The complexation between DNA and polycations with the formation of compacted DNA molecules, and the transport of resulting complexes into the cells are discussed. The data on nanostructuring of hemoglobin using polyfunctional crosslinkers and the data on the use of the obtained nanoparticles as oxygen-transporting blood substitutes are summarized. Using nanodisperse silver stabilized with poly(vinylpyrrolidone) as an example it was demonstrated, that transferring silver into nanodisperse state results in widening its bioactivity.

[Complex formation of cholesterol-containing polymers in water solutions].

The dynamic light scattering method was used to study the process of complex formation in water solutions with cholesterol-containing polymers of vinylsaccharide 2-deoxy-2-methacrylamido-D-glucose (double and triple copolymers) in the different solution/polymer mole ratio. Compared to the initial triple cholesterol-containing copolymer the conditions of compaction of the complex formed are found.

[Association-dissociation of molecules of hemoglobin and polymeric hemoglobin in solutions].

The process of association-dissociation of hemoglobin molecules into dimers of its subunits in water-saline solutions is studied by the method of gel-penetrating chromatography and ultrafiltration. The quantitative assessment of stabilization of quaternary structure of hemoglobin in chemically bound polymer derivative in comparison with native peptide on the basis of building differential concentration curves is conducted for the first time. By the method of atomic-force spectroscopy, the morphology of nanoparticles of hemoglobin and its modified polymeric derivative is studied.

[Antimicrobial activity of carbon fiber fabric modified with a polymer-gentamicin complex].

Modified and unmodified carbon fiber supports were treated with solutions of a polymer-gentamicin complex, possessing high antimicrobial activity and low toxicity. It was found that the antimicrobial activity of modified carbon fiber fabrics depended on the nature of the support and on the immobilization conditions. The highest antimicrobial activity was observed with phosphorus-containing carbon fiber ion exchanger in salt form.

[DNA complexes with polycations used for delivery of DNA into cells].

The formation and physicochemical properties of high-molecular thymus and plasmid DNA complexes with synthetic polymers based on (dimethyl-amino)ethyl methacrylate (DMAEM), (diethyl-amino)ethyl methacrylate (DEAEM), and polyvinyl amine (PVA) were investigated in solutions of different ionic strength by low-gradient viscometry, electrophoresis, circular dichroism, spectrophotometry, and dynamic light scattering. The toxicity of complexes in T98G cells was studied. It was shown that, when the ratio of polycations to DNA charged groups concentration (N+/P) reaches values > 1, DNA condensation occurs. It is accompanied by increasing optical density of solutions. Changes in DNA size after condensation were estimated. Phase diagrams of systems DNA/polycation in the presence of NaCl were obtained. It was shown by MTT-analysis that DNA complexes with polycations in the range of concentrations used have low toxicity.

DNA-polycation complexes: effect of polycation structure on physico-chemical and biological properties.

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 (beta-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.

[Derivatives of N-amidinoproline and their use in conventional and solid phase peptide synthesis].

N-Amidinoproline, a hybrid structure modeling key features of the Arg-Pro sequence, was synthesized. The activation of carboxyl group of free N-amidinoproline was found to result in the formation of a cyclic side product, whose structure was confirmed by ESI MS, 1H NMR, and 13C NMR spectra. The preparation of N-(mesitylenesulfonylamidino)-L-proline using the mesitylenesulfonyl derivative of 2-methylisourea was demonstrated to be accompanied by partial racemization. The target product was synthesized by modification of N-amidinoproline by mesitylenesulfonyl chloride. The possibility of using N-amidinoproline in the N-terminal modification of a peptide chain was shown by the example of synthesis of an analogue of the 95-98 fragment of fibrinogen alpha chain.

[A short test for potential carcinogenicity of water soluble synthetic polymers].

The effect of synthetic water-soluble polymer with different structure on the appearance in SZNA mice of carcinogen-protein adducts (CPA) containing endogenous carcinogen, 3-oxyanthranilic acid (3-OAA), was investigated. CPA containing 3-OAA (3-OAA-CPA) were detected during the administration of 24 of 30 investigated polymers. The induction of 3-OAA-CPA and the character of their distribution in the organism (in all investigated tissues: serum, extracts of liver, spleen, lungs and kidneys tissues or in single tissues) depended on the chemical structure of polymers. It is concluded, that synthetic polymers represent potential cancerogenic danger, because their administration causes formation of 3-OAA-CPA in the organism of animals.

Cellulose materials modified by antiseptics and their antimicrobial properties.

Adsorption properties of dressing cellulose materials with respect to surfactant antiseptics were studied. These antiseptics are a complex of the copolymer of N-vinylpyrrolidone and crotonic acid with dimethylbenzylalkylammonium chloride (a synthetic polymer with a wide spectrum of antimicrobial effect) and its low molecular weight analogue (dimethylbenzylalkylammonium chloride). It was established that cellulose materials reversibly adsorb mentioned surfactant antiseptics depending on their concentration in the initial solutions. Maximum release of surfactant antiseptics is achieved at solutions at pH = 7.0. Microbiological tests of cellulose materials modified by antiseptics have shown that they exhibit antimicrobial activity. These results can be used in medical practice in clinics for imparting antimicrobial properties to dressing materials.

Anti-inflammatory and antishock water-soluble polyesters of glucocorticoids with low level systemic toxicity.

PURPOSE: The objective of this study was to evaluate the pharmacological activity of glucocorticoid hormones incorporated into the structure of water-soluble carbochain polymers via the esterified 21-CH2OH group. METHODS: Polymer analogs of glucocorticoids were prepared by radical copolymerization of 1-vinyl-2-pyrrolidone with cortisol or dexamethasone 21-crotonates and crotonic acid or 2-(diethylamino) ethylcrontonate which served as ionogenic comonomers. Anti-inflammatory, immunosuppressive and catabolic activities for ionogenic tertiary copolymers and previously prepared non-ionogenic binary copolymers were evaluated in standard animal models. The antishock activity of some of the copolymers was evaluated using the "declamping shock" model. RESULTS: Water-soluble tertiary copolymers with a steroid content up to 14 mol% and an intrinsic viscosity up to 0.30 dl/g in ethanol were synthesized. It was shown that the copolymers were stable in aqueous solutions at pH 5.2-7.3. All of the polymers studied suppressed inflammatory reactions at the level of free hormones when administered interperitoneally. The antishock activity was considerably higher compared to free steroids. The copolymers, unlike unmodified glucocorticoids, did not influence the physical development of young animals. They also caused much lower thymus hypotrophy than free hormones. No clear effect of the presence and nature of ionogenic units in copolymers on the pharmacological performance of the copolymers was detected. CONCLUSIONS: The water-soluble polymers bearing glucocorticoid 21-residues in the side chains retain the anti-inflammatory activity of free steroids and exhibit a higher antishock, a lower immunosuppressive and no catabolic effect.

[Immunogenic properties of neomycin conjugates with macromolecular carriers]. / Issledovanie immunogennykh svoistv kon"iugatov antibiotika neomitsina s makromolekuliarnym nositeliami.

To obtain diagnostic antibodies to neomycin, immunogenic properties of the neomycin conjugates with macromolecular carriers were studied. Bovine serum albumin and copolymers of N-vinylpyrrolidone with crotonic acid and N-hydroxyphthalimide ether of crotonic acid were used as carriers. It was shown that immunization of mice by the conjugates in combination with Freund's adjuvant resulted in production of neomycin antibodies, the titer being 1/80 to 1/130. When the antibiotic conjugates with the copolymers of N-vinylpyrrolidone were used and not the neomycin conjugates with the carrier of the protein nature, the neomycin antibodies were produced in the absence of Freund's full adjuvant. With the use of the isolated antibodies to neomycin a method for indirect solid phase enzyme immunoassay of neomycin was developed at the minimum detectable level of 25 ng/ml.

Conjugates of benzidine with a ternary phenol-containing copolymer of N-vinylpyrrolidone as test antigens for the detection of benzidine in human serum.

Water-soluble polymeric amide and azo derivatives of benzidine, based on the terpolymer N-vinylpyrrolidone-crotonic acid-p-crotonoylaminophenol, which possesses adjuvant activity, were synthesized. By means of a double diffusion reaction in agar and a complement-binding reaction it was found that immunization of rabbits with the benzidine-polymer antigens (with or without complete Freund's adjuvant) led to the formation of highly specific antibodies against the hapten benzidine. Sera from rabbits immunized with these conjugates of benzidine may thus be used for the detection of benzidine in the sera of workers exposed to this chemical.

[Antineoplastic and immunostimulating effects of several N-vinylpyrrolidone co(ter)polymers in C3HA strain mice with hepatoma 22a]. / Protivoopukholevoe i immunostimuliruiushchee deistvie nekotorykh co(ter)polimerov N-vinilpirrolidona na myshei linii C3HA s gepatomoi 22a.

The antitumor and immunoadjuvant action of water-soluble N-vinylpyrrolidone co(ter)polymers of different chemical structure is studied. It is established that terpolymer N-vinyl-pyrrolidone (VP)--crotonic acid (CA)--n-crotonoylaminophenol inhibiting the growth of hepatoma 22a by 50-60% possesses an antitumoral action, while copolymer VP-CA has an immunoadjuvant action. These properties of co(ter)polymers are due to their chemical structure and molecular weight, but they do not always correlate between themselves.