Peptidomimetic macrocycles

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new peptidomimetic macrocycles and methods for using these macrocycles to modulate p53 and/or HDM2, HDMX activity.

EFFECT: producing new compounds.

33 cl, 8 dwg, 4 tbl, 13 ex

 



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a cyclic compound containing the amino acid sequence GQRETPEGAEAKPWY in addition to one or two additive amino acids, and having no C-terminal carboxyl group and/or N-terminal amino group, where one of the amino acids is a synthetic amino acid, and wherein a ring is closed between a side chain of one amino acid and a C-terminal of the other amino acid, or the ring is closed by the synthetic amino acid; a method for preparing and using it to regulate vector ion channels for treating the diseases related to the pulmonary function, and for treating oedemas.

EFFECT: preparing the composition for treating the diseases related to the pulmonary function, and for treating oedemas.

16 cl, 16 dwg, 2 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: method includes steps of: (1) extracting fermentation broth containing a compound of formula I or a salt thereof to obtain an extract 1 after filtering and centrifuging; (2) diluting or concentrating the extract 1 in a vacuum with reduction of organic solvent content to obtain an extract 2; (3) feeding the extract 2 into a macroporous adsorption resin; (4) washing the macroporous adsorption resin with water or a mixture of water and an organic solvent as a washing solution and (5) eluting the compound of formula I from the macroporous adsorption resin with the mixture of water and organic solvent as an eluent.

EFFECT: method enables to use a smaller amount of organic solvent and improves purity of the collected compound of formula I.

8 cl, 2 dwg, 2 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: method includes steps of: (1) feeding a raw compound of formula I into a macroporous adsorption resin; (2) washing the macroporous adsorption resin with water, an organic solvent or a mixed solution of an organic solvent and water as the washing liquid; and (3) elution of the compound of formula I from the macroporous adsorption resin with water, an organic solvent or a mixed solution of an organic solvent and water as an eluent, where at step (1) the solution containing a raw compound of formula I contains ionisable salts; and the macroporous adsorption resin is selected from a nonpolar aromatic adsorption resin polymerised from styrene and divinyl benzene, or a methacrylic adsorption resin of medium polarity with methacrylate residues in the structure.

EFFECT: purification method has the advantages of using a small amount of organic solvents without using silica gel and low environmental impact; the collected compound also has better purity compared to previous methods.

13 cl, 2 tbl, 2 dwg, 8 ex

FIELD: chemistry.

SUBSTANCE: disclosed is a method of purifying a compound of formula 1 which includes the following steps: (1) adding a raw compound 1 to a macroporous adsorption resin, (2) washing the macroporous adsorption resin with an aqueous solution, an organic solvent or a mixed solution of an organic solvent and water, (3) elution using the aqueous solution, organic solvent or mixed solution of an organic solvent and water.

EFFECT: improved method.

9 cl, 7 dwg, 12 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of purifying daptomycin, which includes steps a) loading partially purified daptomycin into an anion-exchange chromatographic column and subsequent purification steps b) and c) in reversed-phase chromatographic columns, where the elution buffer at step a) is a monovalent salt solution and the elution buffer at step b) and c) is an aqueous alcohol.

EFFECT: improved method.

16 cl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel intermediate compounds of the given formula or acid-addition salts or solvates thereof, where R1 is -(CO)NH2, -CH2NH2 or -CN; R2=R3=H or R2 and R3 together form a cyclic boronate or a boric acid ester; X is an auxiliary group consisting of i) a five- or six-member heterocyclic aromatic ring containing at least one N atom, which is part of an imino group, where said N atom forms a bonding site for a cyclohexapetide ring and ii) tetrazolyl, for which the nitrogen forms a bonding site for a cyclohexapeptide ring. The present invention also relates to a method of producing caspofungin using said intermediate compounds.

.

EFFECT: improved method.

11 cl, 9 ex

FIELD: chemistry.

SUBSTANCE: polypeptide compounds contain cyclohexyl methyl amino groups or piperidyl methyl amino groups in the structure.

EFFECT: excellent activity against deep fungal infection.

16 cl, 66 tbl, 45 ex

FIELD: medicine.

SUBSTANCE: invention refers to peptide melanocortin receptor ligands, particularly melanocortin-4 receptor.

EFFECT: higher clinical effectiveness in diseases reacting on activation of the given receptor, eg obesity, diabetes and sexual dysfunction.

13 cl, 7 dwg, 7 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: invention refers to compounds of general formula

(VI)

which exhibit antibacterial activity and can be used for controlling bacterial infections.

EFFECT: higher antibacterial activity of the compound.

6 cl, 1 tbl, 26 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel purified compound PM 181104 of formula I

(with molecular weight 1514 and molecular formula C69H66N18O13S5), pharmaceutically acceptable salts thereof, methods for synthesis via fermentation of a microorganism of the type Kocuria (ZMA B-1 / MTCC 5269), as well as pharmaceutical compositions.

EFFECT: high efficiency of using the composition to produce a medicinal agent for treating bacterial infections.

20 cl, 4 dwg, 4 tbl, 16 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to biotechnology and provides a α1,6-glucan-containing compound of Helicobacter pylori. The present invention also discloses a conjugate for inducing immune response against H.pylori, which contains said compound conjugated with a carrier protein. The present invention also discloses an immunogenic composition, use of said composition and a method of inducing immune response against H.pylori using said composition. The present invention also discloses immune serum for neutralising H.pylori in mammals, which is obtained by immunising said mammal with an immunogenic composition containing said immunogenic composition. The present invention discloses an antibody which recognises said α1,6-glucan-containing compound of H.pylori, use of said antibody and a method of inducing complement-mediated bacteriolysis of H.pylori strains which express α1,6-glucan using said antibody.

EFFECT: invention improves the effectiveness of immunogenic compositions against Hpylori.

27 cl, 8 dwg, 21 tbl, 11 ex

FIELD: chemistry.

SUBSTANCE: invention relates to field of biotechnology, namely to internalisation of therapeutic molecules into cell, and can be applied in medicine. Obtained is composition for delivering molecules of nucleic acids into cells, containing at least one peptide with at least 92% identity to GAAEAAARVYDLGLRRLRQRRRLRRERVRA (SEQ ID NO: 2); IREIMEKFGKQPVSLPARRLKLRGRKRRQR (SEQ ID NO: 3); or YLKVVRKHHRVIAGQFFGHHHTDSFRMLYD (SEQ ID NO: 4), bound to one or several molecules of nucleic acids.

EFFECT: invention makes it possible to increase efficiency of delivery of molecules of nucleic acids into mammalian cell due to peptide, capable of internalisation into mammalian cell with efficiency, constituting at least 200% of efficiency of internalisation of peptide TAT, which has amino acid sequence GRKKRRQRRRPPQ (SEQ ID NO: 1).

8 cl, 16 dwg, 1 tbl, 8 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to biotechnology and represents an immunogenic composition for preventing and treating cancer diseases, which contains the non-functional BORIS protein, a sequence of which is free from the zinc finger protein. The present invention also discloses an immunotherapeutic cancer composition containing the above non-functional BORIS protein or a bacterial, mammalian or yeast cell, or a viral particle able to express the above non-functional BORIS protein. The present invention also discloses a method for immunising a patient by administering an effective amount of the above immunotherapeutic composition, as well as using the above immunotherapeutic composition for preparing the cancer vaccine.

EFFECT: invention enables increasing the efficacy of the immunoprophylactic and therapeutic cancer vaccine.

22 cl, 7 dwg, 2 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention refers to biotechnology, specifically to VEGF-A specific binding proteins, and can be used in medicine for treating pathological angiogenesis in mammals. The antiangiogenic protein contains one ankyrin recurrent domain consisting of a N-terminal capping module of ankyrin recurrence, a recurrent module presented by an ankyrin recurrent motif of the sequence 1D23G4TPLHLAA56GH7EIVEVLLK8GADVNA (SEQ ID NO:5), wherein 1 represents an amino acid residue specified in A, N, R, V, Y, E, H, I, K, L, Q, S and T; 2 is specified in S, A, N, R, D, F, L, P, T and Y; 3 is specified in T, V, S, A, L and F; 4 is specified in W, F and H; 5 is specified in P, I, A, L, S, T, V and Y; 6 is specified in W, F, I, L, T and V; 7 is specified in L or P and 8 is specified in A, H, N and Y; a recurrent module presented by an ankyrin recurrent motif of the sequence 1D23G4TPLHLAA56GHLEIVEVLLK7GADVNA (SEQ ID NO:1), wherein 1, 2, 3, 4, 5, 6 and 7 independently represents an amino acid residue specified in the group of A, D, E, F, H, I, K, L, M, N, Q, R, S, T, V, W and Y, and a C-terminal capping module.

EFFECT: invention enables producing an antiangiogenic binding VEGF-A165 with Kd less than 10-7 M protein, which inhibits binding VEGF-A165 to VEGFR-2.

12 cl, 4 dwg, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the field of biotechnology, namely to obtaining oligopeptide compounds, containing a motive, interacting with a proliferating cell nuclear antigen (PCNA) and can be used in medicine. The oligopeptide compound consists of 14-70 amino acids and contains. a PCNA-interacting motive, representing [K/R]-[F/Y/W]-[L/I/V/A]-[L/I/V/A]-[K/R], at least one signal sequence of nuclear localisation and at least one signal sequence of penetration into a cell, with the PCNA-interacting motive being located towards an N-end relative to the signal sequence.

EFFECT: invention makes it possible to carry out the efficient treatment of hyperproliferative disorders by the application of the oligopeptide compound in cyctostatic therapy or in radiotherapy as a sensitising substance.

34 cl, 6 dwg, 4 tbl, 8 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to biotechnology, more specifically to MUC1 cytoplasmic domain peptides, and can be used in the anticancer therapy. A method for inhibiting MUC1-positive cancer cell in an individual involves administering into an individual the MUC1-peptide of the length of at least 6 sequential MUC1 residues and no more than 20 sequential MUC1residues and containing the sequence CQCRRK, wherein the amino terminal cysteine from CQCRRK is closed at its NH2 terminal by at least one amino acid residue, which shall not conform with the native transmembrane sequence MUC-1. Alternatively, there can be used MUC-1 peptide of the length of at least sequential MUC1 residues and no more than 20 sequential MUC1 residues, which contains the sequence CQCRRK with all amino acid residues of the above peptide being D-amino acids.

EFFECT: invention enables inhibiting MUC1oligomerisation effectively and inducing the tumour cell apoptosis and the tumour tissue necrosis in vivo.

80 cl, 16 dwg, 1 tbl, 3 ex

FIELD: metallurgy.

SUBSTANCE: invention relates to casein succinylate of iron (III) wherein iron content varies from 4.5 wt % to 7 wt %, water solubility exceeds 92% while phosphorus-to-nitrogen ratio exceeds 5 wt %.

EFFECT: additionally, invention relates to production of iron (III) and to pharmaceutical composition containing casein succinylate of iron (III).

17 cl, 4 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: presented group of inventions refers to biotechnology, and concerns a DLK1-Fc fused protein and using it for the metastases inhibition, a polynucleotide coding such a protein, an expression vector containing the polynucleotide, a host cell producing the above fused protein, a method for producing the fused protein by culturing the above host cell, a composition containing the above fused protein, and a method for the metastases inhibition. The characterised fused protein contains a DLK1 extracellular soluble domain consisting of the amino acid sequence SEQ ID NO:4 and Fc domain of a human antibody.

EFFECT: group of inventions can be used for preparing a therapeutic agent for reduction of cancer cell migration and the metastases inhibition.

11 cl, 36 dwg, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to biochemistry. Application of a fused protein to obtain a composition for the body weight reduction is described. The fused protein contains a domain of transduction, a signal of mitochondrial localisation and a domain of a mitochondrial factor of transcription A, binding polynucleotide (TFAM), containing a group with high mobility. Methods of treating obesity by means of the said protein are described.

EFFECT: invention extends an arsenal of means for treating obesity.

9 cl, 5 dwg, 2 ex

FIELD: biotechnology.

SUBSTANCE: invention relates to a method of production of casein calcium chloride of technical casein by precipitation, and can be used in microbiological studies for production of components of storing media of cultures of microorganisms, and also production of calcium co-precipitates for food industry.

EFFECT: improvement of the method.

2 cl, 1 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to biotechnology and provides a α1,6-glucan-containing compound of Helicobacter pylori. The present invention also discloses a conjugate for inducing immune response against H.pylori, which contains said compound conjugated with a carrier protein. The present invention also discloses an immunogenic composition, use of said composition and a method of inducing immune response against H.pylori using said composition. The present invention also discloses immune serum for neutralising H.pylori in mammals, which is obtained by immunising said mammal with an immunogenic composition containing said immunogenic composition. The present invention discloses an antibody which recognises said α1,6-glucan-containing compound of H.pylori, use of said antibody and a method of inducing complement-mediated bacteriolysis of H.pylori strains which express α1,6-glucan using said antibody.

EFFECT: invention improves the effectiveness of immunogenic compositions against Hpylori.

27 cl, 8 dwg, 21 tbl, 11 ex

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