Derivatives aminomethanesulfonic as substrates for the determination of active protein c (aps)
(57) Abstract:The invention relates to Bioorganic chemistry, namely to new tribromide 6-(glycyl-glycyl - L-arginyl - L-arginyl)aminonaphthalene - 1-cyclohexylsulfamate and 6-(benzyloxycarbonylglycine-glycyl - L-arginyl - L-arginyl)aminonaphthalene - 1-cyclohexylsulfamic. The aim of the invention is to increase the selectivity. The essence of it is that new substrates rapidly hydrolyzed by the enzyme APS, and slowly thrombin. Their 10% hydrolysis by the enzyme APS in 830 - 180 times shorter than thrombin. For evidence of the positive effect calculate constants Michael-Menten Kmand catalytic Kcatand the ratio of these constants define ~ 103- one superiority of the proposed compounds in comparison with the prototype. These features allow to use them as substrates to determine the speed of production of the APS by activation of protein C by thrombin. 6 tab., 3 Il.
FIELD: medicine, immunology, peptides.
SUBSTANCE: invention relates to a new composition of biologically active substances. Invention proposes the composition comprising of peptides of the formula: Arg-Gly-Asp and H-Tyr-X-Y-Glu-OH wherein X means Gln and/or Glu; Y means Cys(acm) and/or Cys that elicits ability to inhibit the proliferative response for phytohemagglutinin, to induce the suppressive activity of mononuclear cells and ability of peptides to induce secretion of immunosuppressive cytokines of grouth-transforming factor-β1 and interleukin-10 (IL-10). The composition can be prepared by a simple procedure.
EFFECT: valuable biological properties of composition.
3 cl, 16 tbl, 9 ex
FIELD: organic chemistry, medicine.
SUBSTANCE: invention represents ligands MC-4 and/or MC-3 of the formula (I): , wherein X means hydrogen atom, -OR1, -NR1R1' and -CHR1R1' wherein R1 and R1' are taken among the group: hydrogen atom, (C1-C6)-alkyl and acyl; (1) each R2 is taken independently among the group: hydrogen atom, (C1-C6)-alkyl; or (2) (a) R2 bound with carbon atom that is bound with X and Z1 and substitute R5 can be optionally bound to form carbocyclic or heterocyclic ring that is condensed with phenyl ring J; or (b) R2 bound with carbon atom that is bound with ring Ar can be bound with R7 to form ring condensed with ring Ar; each among Z1, Z2 and Z3 is taken independently from the following groups: -N(R3e)C(R3)(R3a)-, -C(R3)(R3a)N(R3e)-, -C(O)N(R3d)-, -N(R3d)C(O)-, -C(R3)(R3a)C(R3b)(R3c)-, -SO2N(R3d)- and -N(R3d)SO2- wherein each among R3, R3a, R3b and R3c, R3d, R3e when presents is taken independently among hydrogen atom and (C1-C6)-alkyl; p is a whole number from 0 to 5 wherein when p above 0 then R4 and R4' are taken among hydrogen atom, (C1-C6)-alkyl and aryl; R5 represents 5 substitutes in phenyl ring J wherein each R5 is taken among hydrogen atom, hydroxy-, halogen atom, thiol, -OR12, -N(R12)(R12'), (C1-C6)-alkyl, nitro-, aryl wherein R12 and R12' are taken among hydrogen atom and (C1-C6)-alkyl; or two substitutes R5 can be bound optionally to form carbocyclic or heterocyclic ring that is condensed with phenyl ring J; q = 0, 1, 2, 3, 4 or 5 wherein when q above 0 then R6 and R6' are taken among hydrogen atom and (C1-C6)-alkyl; Ar is taken among the group consisting of phenyl, thiophene, furan, oxazole, thiazole, pyrrole and pyridine; R7 are substitutes at ring Ar wherein each R7 is taken among hydrogen, halogen atom, -NR13R13', (C1-C6)-alkyl and nitro- wherein R13 and R13' are taken among hydrogen atom and (C1-C6)-alkyl; r is a whole number from 0 to 7 wherein when r is above 0 then R8 and R8' are taken among hydrogen atom and (C1-C6)-alkyl; B is taken among -N(R14)C(=NR15)NR16R17, -NR20R21, heteroaryl ring and heterocycloalkyl ring wherein R14-R17, R20 and R21 are taken independently among hydrogen atom and (C1-C6)-alkyl; s = 0, 1, 2, 3, 4 or 5 wherein when s is above 0 then R and R9' are taken among hydrogen atom and (C1-C6)-alkyl; R10 is taken among the group consisting of optionally substituted bicyclic aryl ring and optionally substituted bicyclic heteroaryl ring; D is taken among hydrogen atom, amino- and -C(O)R11 wherein R11 is taken among the following group: hydroxy-, alkoxy-, amino-, alkylamino-, -N(R19)CH2C(O)NH2 wherein R19 represents (C1-C6)-alkyl, -NHCH2CH2OH and -N(CH3)CH2CH2OH, or its isomers, salts, hydrates or biohydrolysable ester, amide or imide.
EFFECT: valuable medicinal properties of compounds.
18 cl, 107 ex
FIELD: peptides, pharmacy.
SUBSTANCE: invention relates to low-molecular derivatives of peptides that are able to act as inhibitors in interaction between laminine and nidogen (interactions laminine/nidogen). Also, invention relates to a method for their preparing, pharmaceutical composition prepared on thereof and their using for preparing pharmaceutical agents, and for identification of inhibitors in interaction laminine/nidogen.
EFFECT: valuable properties of peptides.
5 cl, 12 dwg
FIELD: medicine, chemistry of peptides, amino acids.
SUBSTANCE: invention relates to novel biologically active substances. Invention proposes the novel composition comprising peptides of the formula: H-Arg-Gly-Asp-OH and H-Tyr-X-Y-Glu-OH wherein X means Gln and/or Glu; Y means Cys(acm) and/or Cys. The composition shows ability to inhibit proliferative activity of mononuclear cells, to induce suppressive activity and their ability for secretion of cytokines TNF-1β (tumor necrosis factor-1β) and IL-10 (interleukin-10 ).
EFFECT: simplified method for preparing composition, valuable medicinal properties of composition.
4 cl, 16 tbl, 9 ex
FIELD: biotechnology, medicine, oncology.
SUBSTANCE: invention proposes peptide of the structure Tyr-Ser-Leu and a pharmaceutical composition based on thereof that is used for stimulating antitumor immune response. Also, invention proposes methods for treatment of mammal and for modulation of the immune response. Proposed inventions expand assortment of agents used in treatment of cancer diseases.
EFFECT: valuable medicinal properties of peptide and pharmaceutical composition.
20 cl, 48 tbl
FIELD: pharmaceutical chemistry, chemistry of peptides, hormones.
SUBSTANCE: invention relates to a method for preparing analogs of adrenocorticotropic hormone (ACTH) (4-10) possessing neurotropic activity. Method for preparing analogs of adrenocorticotropic hormone (ACTH), a sequence (4-10), of the general formula (I): A-Glu-His-Phe-Pro-Gly-Pro-OH (I) wherein A means hydrogen atom (H), Met, Met(O), Lys, Ser, Trp, Ala, Gly, Thr is carried out by liquid-phase method by step-by-step splicing peptide chain beginning from C-terminal protected tetrapeptide of the formula: H-Phe-Pro-Gly-Pro-OH (II) wherein X means a protective group and using corresponding fully protected amino acids in activated form followed by removal of protective groups at each step and purification of the end product by liquid chromatography. Method provides simplifying the process and to enhance the yield of the end product.
EFFECT: improved preparing method.
5 cl, 1 tbl, 5 ex
SUBSTANCE: present invention refers to compounds of Formula II and to methods of immune response suppression, e.g. by inhibition of indirect MHC type II of T-cells activation. Compounds under invention can be applied to treatment or prevention of derangements, such as rheumatoid arthritis and/or multiple sclerosis.
EFFECT: production of compounds which can be used for immune response suppression.
25 cl, 19 dwg, 4 tbl, 22 ex
SUBSTANCE: invention relates to low-molecular derivatives of peptides which are used for preparing a pharmaceutical agent which inhibits laminin/nidogen reaction.
EFFECT: increased effectiveness of compounds.
2 cl, 12 dwg, 2 tbl, 30 ex
SUBSTANCE: invention relates to α',β'-epoxides of peptides of formulae (III) and (IV) which inhibit chymotrypsin-like activity of 20S proteasome.
EFFECT: increased effectiveness of the compounds.
19 cl, 29 ex
FIELD: chemistry; biochemistry.
SUBSTANCE: invention relates to bioengineering and specifically to obtaining biologically active substances of peptide nature, which have growth factor activity towards collagen synthesis stimulation and can be used in medicine. An oligopeptide of general formula A-X1-X2-X3-X4-X5-B (I) is obtained through in silico construction, where A is Ac - acetyl; X1 is G or A or is absent; X2 is P or I, or L, or V, or A; X3 is G; X4 is P or I, or L, or V, or A; X5 is G or A, or is absent and B is OMe - methyl.
EFFECT: invention enables obtaining an oligopeptide with acidic (aFGF) and transformation (TGF-β) growth factor activity towards stimulation of collagen biosynthesis, and expansion of the range of effective therapeutic agents with wound-healing effect, which speed up regeneration of damaged tissue and cicatrisation.
4 dwg, 2 ex
FIELD: medicine, oncology, molecular pharmacology.
SUBSTANCE: invention relates to a method and set for identifying the individual subjected to risk for arising in it the vascular and cancer disease. Method involves stages for the quantitative determination of the analyte concentration, i. e. pepsinogen I (PGI), in serum sample taken in the personal individual; comparison of the analyte concentration determined by the proposed method with a method-specific boundary value for this analyte; determination of the homocysteine concentration in a serum sample taken in this individual. The set comprises the combination of separate components that are necessary for the quantitative determination of the PGI concentration. Method provides the early detection of the possibility for arising the vascular and cancer disease in the patient.
EFFECT: improved method for assay.
FIELD: production methods.
SUBSTANCE: method is based on the capability of defibrotide to increase the fermentation activity of plasmin and foresee the stages: a) making the contact in reactional area defibrotide, plasmin and substrate specific for plasmin which, because of reaction, provides the defined product b) the definition of the amount of obtained product in temporary points.
EFFECT: invention allows to define the biological activity of defibrotide in comparison with standard etalon with height accuracy and big repeatability.
9 cl, 6 dwg, 4 tbl, 1 ex
FIELD: chemistry; biochemistry.
SUBSTANCE: invention relates to biotechnology, specifically to a method of identifying γ-secretase and its inhibitors and can be used in medicine when searching for active compounds for treating Alzheimer's disease. A genetic structure is formed, which codes fused protein, which contains a signal peptide and amino acid sequence GAIIGLMVGGVVIATVIVITLVML. In the obtained fused protein, except the GAIIGLMVGGVVIATVIVITLVML sequence, all sites acting as a signal for endo- or exocytosis, and/or protease splitting site are excluded.
EFFECT: invention allows for highly effective identification of γ-secretase or substances which inhibit its activity by reducing background signal and increasing specificity of the signal.
41 cl, 4 dwg, 17 ex
SUBSTANCE: according to the following stages, flow cytometry is used to detect living cells, damaged cells, VNC cells and dead cells of a microorganism in a tested sample: a) the stage of processing the tested sample with enzyme chosen from lipolytic enzymes and protease with activity to destruct the cells differing from those of the microorganism, colloid protein particles or lipids found in the analysed sample; b) the stage of processing the tested sample with topoisomerase inhibitor and/or DNA-gyrase inhibitor; e) the stage of processing the tested sample been processed at the stages a) and b) with a kernel-dyeing agent, and d) the stage of detecting microorganisms in the tested sample processed by the kernel-dyeing agent with using flow cytometry.
EFFECT: convenient and fast detecting of live microorganisms and identification of the damaged and dead cells in foodstuff and clinical samples.
19 dwg, 8 tbl, 8 ex
SUBSTANCE: there is offered a method for identification of an inhibiting candidate substance which enables inhibits hepsin-activated HGF. The method is based on comparing the degree of activation of pro-HGF substratum in a sample containing hepsin, pro-HGF and the analysed candidate substance, with the degree of activation of pro-HGF substratum in the reference sample who not containing the candidate substance. Also there is offered an agent for inhibiting hepsin and hepatocyte growth factor reaction containing a sequence of Kunitz domain which represents a KD-1 sequence of Kunitz domain HAI-1 or HAI-1B, or one or both Kunitz domains HAI-2.
EFFECT: invention allows identifying physiological hepsin modulators.
6 cl, 14 dwg, 1 tbl, 1 ex
FIELD: food industry.
SUBSTANCE: quantitative food proteins content determination method involves the following operations, sequentially performed: mixing test samples of the substrate and a fermentative substance coupled with a stabilising solution, incubation of the produced mixture at a temperature of 37°C, centrifugation of the fermentative-and-substrate complex and determination of quantitative food proteins content by way of calculation. The fermentative substance is represented by pancreatic juice preliminarily diluted with a stabilising solution down to 50% concentration, the ratio of the solution to the substrate test sample weight equal to 1:10. The prepared mixture incubation is performed during 5-15 minutes. Before quantitative food proteins content determination by way of calculation, the pure liquid fraction volume produced as a result of centrifugation is diluted with the stabilising solution at a ratio of 1:100-200. The food protein quantity is determined as equal to percentage expenditure of protease enzymes in comparison with a reference sample of pancreatic juice solution.
EFFECT: enhanced accuracy of determination of the quantitative food proteins content in food products.
SUBSTANCE: method of predicting efficiency of complex treatment of patients with nasopharyngeal cancer, which includes carrying out two-step course of radial therapy at the background of automyelochemical therapy, lies in the following: before treatment individual activity of enzyme kallikrein is determined in patient's blood plasma, and then on the 1-2 day after the end of the 1 step of complex treatment activity of enzyme kallikrein is determined in patient's blood plasma, and in case of its 2 and more fold reduction with respect to initial individual activity, efficiency of treatment is predicted, and in case if it reduces by less than 2 times, absence of clinical effect is predicted.
EFFECT: method ensures possibility of objective assessment of individual response to complex treatment and, in case of necessity, timely change of therapeutic mode.
SUBSTANCE: there are presented a method and a kit for enzyme-linked thrombin-binding assay on C1 inhibitor functional activity. The method implies thrombin sorption in microplate wells, introduction of test samples containing the functionally active C1 inhibitor to be analysed, incubation that involves C1 inhibitor binding to thrombin, and measurement of the C1 inhibitor-bound amount by an enzyme conjugate with antibodies and a substrate of said enzyme. The kit comprises a flat-bottomed microplate with the sorbed preparation of thrombin, the enzyme conjugate with the human C1 inhibitor antibodies, a substrate buffer and a reference for measuring the active C1 inhibitor.
EFFECT: group of inventions provides the novel method and kit for enzyme-linked thrombin-binding assay on C1 inhibitor functional activity.
2 cl, 2 dwg, 2 ex
SUBSTANCE: invention relates to molecular biology and genetics. Disclosed is a method for qualitative and quantitative analysis of lipids that are strongly bound with genomic DNA, which comprises steps of isolating genomic DNA bound with lipids from cells using a detergent method, hydrolysis of DNA with a hydrolysing enzyme, separating lipids from the chloroform-methanol-water mixture at 37°C, evaporating the solvent, stabilising lipids with 2,6-di-tert-butyl-p-cresol, mixing the lipids with TMSH, chromatography with a gas chromatograph, followed by mass spectrometry.
EFFECT: method can be used to decode the lipid code of genomic DNA, ie, to determine the area of localisation of lipids that are strongly bound with genomic DNA for research and therapeutic purposes.