Immunocytokines possessing modulated selectivity
FIELD: chemical-pharmaceutical industry, proteins.
SUBSTANCE: invention concerns to cytokine-containing fused proteins showing the enhanced therapeutic index, and methods for enhancing the therapeutic index of these fused proteins. Fused proteins are able for binding with cytokine receptors of more one type expressed on cells and to bind with cells of more one type also. Except for, fused proteins possess a half-time value in blood stream of a patient as compared with that of corresponding natural cytokines.
EFFECT: improved and valuable properties of cytokines.
21 cl, 3 tbl, 11 ex
FIELD: molecular biology, genetic engineering, biochemistry.
SUBSTANCE: invention relates to polynucleotides optimized for expression in plants and encoding processing enzymes. Polynucleotides encode mesophilic, thermophilic or hyperthermophilic enzymes that are activated under conditions suitable for interaction with a necessary substrate. Incorporation of these polynucleotides into the plant genome results to preparing "self-processing" transgenic plants wherein their parts, for example, grain, fruit or seed express one or more indicated enzymes and have the varied composition. Autoprocessing plants can be used, for example, for preparing foodstuffs eliciting improved taste.
EFFECT: improved and valuable biological properties of plants.
29 cl, 23 dwg, 6 tbl, 41 ex
FIELD: biology, in particular gene engineering, microbiological industry, production of new lactam antibiotics.
SUBSTANCE: constructed is recombinant plasmid of pVR1 expression containing DNA fragment which encodes functionally active hybrid protein (DAOcbd), comprising D-amino acid oxydase of Trigonopsis variabilis BKM Y-2601 strain and chitin-coupling domain of A1 Bacillus circulans domain. As a result of transformation of E.coli strain with disclosed recombinant plasmid and selection of transformed clones new Escherichia coli strain C 41 (DE3)/pVR1 as producer of DAOcbd providing high yield of reconbinant enzyme is obtained. Said active DAO in combination with chitin-coupling domain enables purification of target protein wherein in purification process immobilized enzyme form is obtained.
EFFECT: improved method for purification of target proteins.
3 cl, 3 dwg, 2 tbl, 5 ex
FIELD: medicine, biotechnology, pharmacy.
SUBSTANCE: invention relates to exchangers of ligand/receptor specificity delivering antibodies to receptors on pathogen. In particular, invention describes variants related to manufacturing and using exchangers of ligand/receptor specificity. Exchangers comprise at least one specificity domain containing ligand for receptor wherein ligand is not antibody or its part, and at least one antigenic domain combined with abovementioned specificity domain wherein antigenic domain comprises epitope of pathogen or toxin. Advantage of the invention involves enhanced specificity in delivery of drug.
EFFECT: improved and valuable properties of exchangers.
30 cl, 5 tbl, 6 ex
FIELD: medicine, oncology, peptides.
SUBSTANCE: invention relates to a chimeric protein used in treatment of malignant lymphomas. Invention proposes chimeric protein consisting of two peptides representing inhibitor of cyclin kinases as an active fragment p16INK4a with amino acid sequence 84-13 or 84-106 as a therapeutic agent and the second peptide VP22 with sequence 140-301 of virus herpes simplex as a transporting agent. Advantage of the invention involves the development of preparation of high effectiveness of penetration into cells and possessing cytostatic and cytotoxic effects.
EFFECT: valuable medicinal properties of chimeric protein.
1 dwg, 2 ex
FIELD: biotechnology, medicine.
SUBSTANCE: Pcup1-Aβ-SUS35MC hybrid gene is produced on the base of CUP1 promoter, sequence encoding of full-length human amyloid beta (Aβ) peptide, sequence encoding of M and C domains of Sup35 protein of Saccharomyces cerevisiae, and translation terminating sequence.
EFFECT: method for scale screening of Aβ-peptide aggregation regulating agents.
FIELD: medicine, biotechnology.
SUBSTANCE: invention relates to the development of a recombinant fused protein consisting of an oncoprotein E7 VPCH 11 type with a sequence SEQ № 2 and protein of "heat shock" Hsp 70 from M. tuberculosis cells prepared by using plasmid pQE30-E711-dnaK in E. coli cells. The preparation is used against relapsing human papillovirus comprises the recombinant fused protein in the effective amount and a pharmaceutically acceptable carrier. Method for immunotherapy of relapsing larynx papillomatosis involves intracutaneous administration of indicated preparation in a patient. The advantage of invention involves the development of a novel preparation showing improved immunological indices. Proposed preparative formulations can be used in immunotherapy of relapsing larynx papillomatosis in humans.
EFFECT: valuable medicinal properties of protein, improved method for treatment.
3 cl, 6 dwg, 7 ex
FIELD: molecular biology, biochemistry, medicine, oncology.
SUBSTANCE: invention relates to DNA sequences found in analysis of mDNA from squamous carcinoma cellular lines of different origin wherein these DNA sequences represent transcripts from rearranged genes SCCA1 and SCCA2. Result of rearrangement is formation of fused gene consisting of exon 2-7 of gene SCCA1 and exon 8 of gene SCCA2, or exons 2-7 of gene SCCA2 and exon 8 of gene SCCA1. Prepared expressing vectors comprising above said combinations of exons of two genes provide synthesis of corresponding fused protein in host-cell. Proposed sequences of nucleic acids and genetic constructions based on thereof represent novel agents for diagnosis squamous carcinomas.
EFFECT: valuable biological and medicinal properties of transcripts.
8 cl, 9 dwg, 1 tbl, 5 ex
FIELD: genetic engineering, medicine.
SUBSTANCE: invention relates to isolated DNA encoding human peptide related to urocortin and peptide named as urocortin II. These peptides are relative with corticotropin-releasing factor and involves in mechanisms for initiation of hypophysis-suprarenal responses for the stress. Pharmaceutical composition comprising such peptide in combination with acceptable vehicle can be used in treatment of pathophysiological states, such as enhanced body temperature, appetite disorder, congestive cardiac insufficiency, stress, anxiety state and undesirable low levels of ACTH.
EFFECT: valuable medicinal properties of urocortin proteins.
33 cl, 27 dwg, 2 tbl, 16 ex
SUBSTANCE: method involves determining complex formed between HCV anticore antigen and NS3/4a-antibody capable of recognizing both HCV- antigens and antibodies available in sample when using common solid base and solid substrates usable in immunoassay.
EFFECT: high accuracy and sensitivity of hepatitis C diagnosis.
47 cl, 8 dwg, 10 tbl
FIELD: biotechnology, molecular biology, medicine.
SUBSTANCE: invention discloses amino acid sequences of human obesity polypeptide (OB) two isoforms possessing capacity for modulation of animal body mass, their signal peptide-containing precursors and analogues. Polypeptide isoforms are prepared as result of insertions, deletions and amino acid changes that retain activity typical for nonmodified forms of OB-polypeptides, and polyclonal and monoclonal antibodies interaction specifically with new agents modulating the body mass value also. Invention describes DNA sequences encoding these polypeptides and their analogues, vector structures comprising these sequences used for preparing recombinant forms of OB-polypeptides. Invention proposes using new polypeptides and their analogues as an active component in pharmaceutical compositions. Using this invention can promote to solving the problem for providing medicine, veterinary science and animal husbandry with effective agent used for decreasing the body mass value. Invention can be used in medicine for diagnosis and treatment of pathological states associated with disturbance of regulation of human body mass, and in animal husbandry and veterinary science.
EFFECT: valuable biological, medicinal and veterinary properties of polypeptide.
23 cl, 71 dwg, 12 tbl, 17 ex
FIELD: biotechnology, cytokines, pharmacy.
SUBSTANCE: invention relates to a biotechnological method for preparing medicinal agents. Proposed method involves destruction of cells of yeast producer of interleukin-2 (IL-2) wherein synthesis of required protein (IL-2) is carried out, but this producer doesn't secrete this protein, and the following separation of water-insoluble fraction. In the process for preparing water-insoluble components of disturbed cells are retained. The interleukin-2 preparation obtained by this method shows less cost, it is active in oral administration and shows higher activity in some cases as compared with IL-2 preparations purified from components of yeast cells fraction.
EFFECT: improved preparing method, improved and valuable properties of interleukin-2.
13 cl, 2 tbl, 10 ex
FIELD: gene engineering, in particular method for treatment of viral infections.
SUBSTANCE: protein ZCYTO21 has amino acid sequence which is nearly similar to amino acid sequence of interferon-α. Protein and antibodies thereto have antiviral activity and are useful in treatment of hepatitis B and C as well as other diseases.
EFFECT: new protein with antiviral activity.
71 cl, 1 dwg, 6 tbl, 7 ex
FIELD: medicine, immunology, cytokines.
SUBSTANCE: method for preparing interleukin-8 (L-8) from donor blood neutrophiles involves isolating neutrophiles from peripheral blood in double gradient ficol-verografin, bringing about the neutrophile content in cell suspension to the concentration 5 x 106 cells/ml, activation at temperature 37°C for 1 h followed by centrifugation and separation of supernatant containing the end product. For activation the cell suspension of neutrophiles in the concentration 5 x 106/ml of Henx's solution is poured in plastic Petri dishes. Invention provides the development of a simple and available method providing the high level of interleukin-8 (IL-8) from neutrophiles of donor blood not requiring using expensive preparations.
EFFECT: improved preparing method.
FIELD: preparative biochemistry, medicine, pharmacology.
SUBSTANCE: method for purification of interferon proteins is based on using cation-exchange chromatography on a solid matrix. Method is realized at more basic pH value, i. e. at relatively higher pH value corresponding to the isoelectric proteins point, pI, designated for purification. However, at this pH value indicated proteins are remained to be absorbed and therefore method involves using buffer solutions of organic or inorganic salts able to modify the solution ionic strength. Invention provides a simple method for industrial realization of the method and economy availability.
EFFECT: improved purifying method.
8 cl, 1 tbl, 6 ex
FIELD: biotechnology, immunology.
SUBSTANCE: invention proposes hybridomas producing monoclonal antibodies showing specificity to human epiregulin. Invention discloses monoclonal antibody recognizing specifically human epiregulin with the sensitivity limit 10 pg/ml. Also, invention describes methods for specific detection of human epiregulin in a sample in vitro and a method for detection of cells expressing human epiregulin in extracellular fluid in vitro by using monoclonal antibody to human epiregulin. Invention provides a simple and highly sensitive method for detection of human epiregulin that can be used in diagnosis of human epiregulin-expressing tumors.
EFFECT: valuable biological and medicinal properties of antibody and hybridoma.
8 cl, 7 dwg, 8 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to novel compounds of the formula (I) and their pharmaceutically acceptable salts. Proposed compounds possess properties of agonists of receptors activated by peroxisome proliferators (PPAR agonists) and can be used in treatment of such diseases as diabetes mellitus, hypertension, atherosclerotic diseases and others. In the general formula (I) R1 means lower alkyl, monocyclic (C3-C6)-cycloalkyl; R2 means hydrogen atom, halogen atom, lower alkyl, lower alkoxy-group wherein at least one of three radicals R3, R4, R5 or R6 is not hydrogen atom; or R3 and R4 are bound together to form a ring with carbon atoms to which they are bound, and R3 and R4 mean in common -CH=CH-S-, -S-CH=CH-, -CH=CH-CH=CH-, and R5 and R6 are given above; R7 means lower alkyl, lower alkenyl; R8 means hydrogen atom or lower alkyl; n = 1, 2 or 3. Also, invention relates to a pharmaceutical composition based on the invention compounds and to using compounds of the invention in preparing medicinal agents used in treatment and/or prophylaxis of diseases mediated by agonists PPARα and/or PPARγ.
EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.
20 cl, 1 tbl, 13 sch, 71 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to novel compounds of the formulae (I) and (II) and their pharmaceutically acceptable salts and esters wherein each Z1, Z2 and Z3 is chosen from series of (C1-C6)-alkoxy-group, -CH2OCH3 and -CH2OCH2CH3, or one Z1, Z2 or Z3 means hydrogen atom, and each of two others is chosen independently from series (C1-C6)-alkyl, (C1-C6)-alkoxy-group, -Cl, -Br, -F, -CF3, -CH2OCH3, -CH2OCH2CH3, -OCH2CH2R1, -CH2-morpholino, -OR2, -OCH2CF3, -OCH(CH3)CH2OH and -COOQ wherein Q is chosen from series hydrogen atom and (C1-C6)-alkyl, or one of Z1, Z2 or Z3 means hydrogen atom, and two others in common with carbon atoms and in combination with bonds between them and benzene cycle to which they are bound for a cycle chosen from 5- and 6-membered unsaturated cycles and 5- and 6-membered saturated cycles that comprise at least one oxygen atom as heteroatom, and wherein R1 is chosen from series -F, -OCH3, -N(CH3)2 and unsaturated 5-membered cycles comprising at least one nitrogen or oxygen atom as heteroatom, and wherein R2 means 3-6-membered saturated cycle, and each Y1 and Y2 is chosen independently from series -Cl, -Br, -NO2, -C≡N and -C≡CH, and their pharmaceutically acceptable salts and esters and wherein Z4 is chosen from series (C1-C2)-alkyl, (C1-C6)-alkoxy-group, -OH, -SCH3, -CF3, -NO2, -COOQ2, -N(CH3)2, -OCH2-phenyl, -Cl, -Br, -F, -OCH2COQ1, saturated 5- and 6-membered cycles comprising at least one heteroatom wherein heteroatom is chosen from nitrogen (N) and oxygen (O) atom, and wherein Q1 is chosen from series, -OH, -NH2 and -O(C1-C6)-alkyl; Q2 is chosen from series hydrogen atom and (C1-C6)-alkyl; Y1 and Y2 are chosen independently from series -Cl, -Br, -NO2, -C≡N and -C≡CH under condition that if both Y1 and Y2 means -Cl then Z4 doesn't means -Cl, and if both Y1 and Y2 mean -NO2 then Z4 doesn't mean -NO2, and if both Y1 and Y2 mean -CN then Z4 doesn't mean -CN. Also, invention relates to a pharmaceutical composition possessing inhibitory activity with respect to MDM2. Invention provides synthesis of novel biologically active compounds and preparing pharmaceutical compositions based on thereof possessing inhibitory activity with respect to MDM2.
EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.
14 cl, 50 ex
FIELD: medicine, oncology, phytotherapy, chemical-pharmaceutical industry.
SUBSTANCE: invention relates to an agent used for strengthening the immune system of body and prophylaxis of oncological diseases. The composition comprises spotted milk thistle fruits extract (Sylibum marianum (L.) Gaerth), purple coneflower roots and herb extract (Echinacea purpurea L.) and/or oblique sponk extract (Inonotus obliquus (Pers) Pil.) and accessory substances taken in the definite ratio. The composition can be prepared in form of tablet, solid or soft gelatin capsule, liquid infusion and liposomal forms. The composition can comprise starch, aqueous-alcoholic syrup, lactose, magnesium stearate, lecithin, phospholipids in form of liposomes as accessory substances. After intake dosing the composition shows the positive effect on enhancing resistance to unfavorable factors of environment, treatment and prophylaxis of oncological diseases.
EFFECT: valuable medicinal properties of composition.
2 cl, 5 tbl, 3 ex