Oligopeptide having acidic (afgf) and transforming (tgf-β) growth factor activity towards stimulation of collagen biosynthesis
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
The present invention relates to the field of Bioorganic chemistry, biochemistry and medicine, namely to biologically active substances peptide having the activity of growth factors in relation to the promotion of collagenases, and may find application in medicine, veterinary medicine, as well as in experimental biochemistry.
Collagen is the most abundant protein in animal cells and most important molecular participant fibroplasia, i.e. the formation of connective tissue occurring during wound healing. It is present not only in collagen fibers and basal membranes, but mainly in amorphous substance of the connective tissue. Collagenoses stimulated next signal molecules, the main of which are acidic fibroblast growth factor aFGF and transforming growth factor TGF-β .
The fibroblast growth factor acidic aFGF (FGF-1) belongs to the family heparinases proteins, transforming growth factor TGF-β - family of transforming growth factors. It is shown that aFGF  and TGF-β  stimulate the biosynthesis of collagen in vitro.
The present invention is to expand the Arsenal of effective therapeutic agents with wound-healing effect, accelerating the regeneration of damaged tissues, scarring, and other similar processes of restoration of damaged tissues.p> The main technical result that can be obtained by carrying out the present invention is the implementation of this assignment: the creation of new oligopeptides having the activity of growth factors in relation to the stimulation of the biosynthesis of collagen, the General formula I:
where a represents AC;
X1 represents Gly, Ala or absent;
X2 is a Pro, lle, Leu, Val or Ala;
X3 represents Gly;
X4 is a Pro, lle, Leu, Val or Ala;
X5 represents Gly, Ala, or is absent and the
In represents OMe,
the size of the oligopeptides, exhibiting this activity varies from three to pentapeptides. In the formula: AC is acetyl, Gly is glycine, Ala - Ala, Pro is Proline, lle - isoleucine, Leu is leucine, Val is valine, ome - methyl.
In contrast to the production of pure protein synthesis claimed oligopeptides is simplified and low-cost technology that reduces the cost of new drugs, affects their availability and, consequently, extends the possibilities of their application.
The formula proposed oligopeptides was revealed by the results of computer design binding sites of acidic fibroblast growth factor aFGF and transforming growth factor TGF-β with receptors on the surface of stem cells. To the computer design of binding sites aFGF and TGF-β and their receptors was performed using software system , carrying out computer simulation of the spatial structure of protein molecules and the design of low molecular weight compounds responsible for the biological function of a protein.
The following drawings form part of the description of the present invention and are included to further demonstrate certain aspects of the present invention. The present invention can be better understood by reference to one or more of these drawings in combination with the detailed description presented here are specific embodiments of the present invention.
The drawings show:
figure 1 - spatial structure of the fragment of aFGF protein ;
figure 2 - spatial structure of the fragment of acidic fibroblast growth factor aFGF with identified functional site functional sites in each of the two homologous domains of the proteins selected);
3 - dimensional structure of the protein fragment of TGF-β ;
figure 4 - dimensional structure of the protein fragment of TGF-β with identified functional site functional site is highlighted).
In silico design of functional site aFGF on the basis of the spatial structure of the protein aFGF
To implement design and functional website aFGF used a computer program .
The source data for the work the s was the primary and the spatial structure of proteins, imported from the database Protein Data Bank . In the database of the Bank conducted a search of the spatial structure of aFGF. Result for computer design of selected spatial structure aFGF  (figure 1).
Next conducted a computer simulation, which allowed us to identify spatially contiguous amino acid residues located on the surface of the protein globule aFGF and participating in the interaction aFGF with its receptor (figure 2). Based on these results, predicted the formula proposed oligopeptides.
In silico design of functional site of TGF-β on the basis of the spatial structure of the protein TGF-β
To implement design and functional site of TGF-β was used a computer program .
The source data for the work was the primary and the spatial structure of proteins imported from the database Protein Data Bank . In the database of the Bank conducted a search of the spatial structure of TGF-β. Result for computer design of selected spatial structure of TGF-β  (figure 3).
Next conducted a computer simulation, which allowed us to identify spatially contiguous amino acid residues located on the surface of the globule protein TGF-β and participating in the interaction of TGF-β with his Retz what porom (figure 4). Based on these results, predicted the formula proposed oligopeptides.
The identified binding sites are structural analogues of the epitopes defined for aFGF (see example 1), which confirms the activity of the in silico predicted compounds in relation to the stimulation of collagen biosynthesis.
Presented in figure 2 and figure 4 data on computer simulation results, we can conclude that the proposed Oligopeptide represents a functional website aFGF and TGF-β is involved in binding to receptors on the surface of stem cells and stimulating the biosynthesis of collagen. This connection can be used in medicine and veterinary medicine as a means to wound-healing effect, accelerating the regeneration of damaged tissues, scarring, and other similar processes of restoration of damaged tissues.
Sources of information
1. Chesnokova N.P. Infectious process / Nposhnikov [and others]. - M.: Academy of natural Sciences, 2006. - 484 S.
2. Pat. US/08558/9418, MPK7 SC 14/50; AC 31/375; AC 38/18; AC 45/06. Wound healing compositions containing fibroblast growth factor and ascorbic acid / J.C.Geesin, J.S.Gordon. No. EP 19910312105.
3. Rodriguez-Barbero, A. Endoglin Modulation of TGF-β1-Induced Collagen Synthesis is Dependent on ERK 1/2 Activation MARK / A.Rodriguez-Barbero [et al.] // Cell Physiol Biochem. - 2006. - Vol.18. - P.135-142.
4. Shutov IV Computer modeling spatial article shall unjury protein molecules / Iveta, Limonnikova, Vpopovic // Chemistry, structure and function of biomolecules: abstracts of the reports. - Minsk : 2006. - .PR-162.
Oligopeptide having the activity of acidic (aFGF) and transformative (TGF-β) growth factors in relation to the stimulation of the biosynthesis of collagen, the General formula
where a represents AC;
X1 represents G or A, or absent;
X2 represents R, or I, or L, or V, or A;
X3 represents G;
X4 represents R, or I, or L, or V, or A;
X5 represents G or A, or absent and represents OMe,
where AC is acetyl, G is glycine, A - alanine, d - Proline, I - isoleucine, L - leucine, V - valine, OMe - methyl, the size of oligopeptides ranging from three to Pentapeptide.
SUBSTANCE: invention is related medicine and concerns applications of antibodies specifically recognising any prevailing variants of beta-amyloid peptide, Aβ40 and Aβ42, in preparation of a drug applied for prevention and-or treatment of Alzheimer's disease.
EFFECT: invention provides prevention of progression or reduction of symptoms, and/or decrease in amyloid deposition in an individual when administering an immunostimulating dose of peptide or specific antibody.
7 cl, 3 ex, 2 dwg
SUBSTANCE: small peptides of formula X1-X2-X3-X4-X5-X6-X7-R1, containing 7-12 amino acid residues are proposed.
EFFECT: said peptides are MC4 receptor agonists and are therefore useful in treating obesity and related diseases.
31 cl, 2 tbl, 82 ex
SUBSTANCE: present invention concerns a compound representing a selective agonist of a melanocortin-4 receptor of formula: Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (SEQ ID NO:50) and its pharmaceutically acceptable salts, pharmaceutical compositions and methods for application thereof in preparation of drugs.
EFFECT: higher effectiveness of compound application.
20 cl, 8 dwg, 4 tbl, 4 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 concerns preparation of peptide biologically active substances with activity of vascular endothelium growth factor (VEGF) with respect to angiogenesis stimulation, and can be used in medicine. In silico design is used for making oligopeptide of general formula I: A-X1-X2-X3-X4-X5-B (I) where A is Ac; X1 represents K or R; X2 represents either Q, or E, or N or D; X3 represents R or K; X4 represents either T, or F, or S, or L, or is absent, X5 represents To, or R, or is absent, and B represents OMe.
EFFECT: preparation of oligopeptides with VEGF activity, and extension of range of effective therapeutic agents that accelerates neogenesis.
4 dwg, 2 ex
SUBSTANCE: invention relates to biotechnology, specifically to obtaining biologically active substances of peptide nature, with stem cell factor CSF activity towards thymocyte differentiation, and can be used in medicine. An oligopeptide with formula I is obtained through in silico design: A-X1-X2-X3-X4-X5-B (I), where A is Ac; X1 is K or R; X2 is A or G; X3 is S or T; X4 is A, or G, or is absent, X5 is N, or Q, or is absent and B is Ome.
EFFECT: invention allows for obtaining an oligopeptide with stem cell factor CSF activity towards differentiation of immature precursors of T-lymphocytes, and widening the range of effective therapeutic agents for treating myelodysplastic syndrome.
5 dwg, 2 ex
SUBSTANCE: invention refers to the conjugates of formula (V)
or (VI) : wherein X is -CO-NH- or -O-; their use as radiopharmaceuticals, processes for their preparation, and synthetic intermediates used in such processes.
EFFECT: use as radiopharmaceuticals.
25 cl, 15 ex
SUBSTANCE: invention relates to cytotoxic compounds with directional effect, which are peptide derivatives of camtothecin, doxyrubicin and palitaxel, their pharmaceutical compositions and use in making medicinal agents for treating pathological conditions, related to aberrant or undesirable proliferation, migration and/or physiological activity of cells.
EFFECT: agents are highly effective.
43 cl, 79 ex, 1 tbl
SUBSTANCE: invention refers to the method for preparation of the cyclic somostatin analogues of formula I and to the intermediates used in the claimed method. The method is implemented by the cyclisation of somostatin having formula II where R1 is -C2-C6 alkylene -NR3R4, R3 and R4 independently of each other are H or acyl, R2 is , where R5 is phenyl, R11 and R12 independently of each other are amino protective groups. If R1 contains the amino end-group the latter is also protected with amino protective group, if necessary the amino protective group(s) is (are) eliminated and thus obtained compound of formula I is reduced in free or salt form.
EFFECT: improvement of method for preparation of somostatin peptides.
6 cl, 4 ex
SUBSTANCE: invention concerns compounds of the formula (Ia) and their application in radiological pharmaceutical compositions for linking to receptors associated with angiogenesis.
EFFECT: possible application in diagnostics or therapy, eg for malignant or cardiac diseases, endometriosis, inflammatory diseases, rheumatoid arthritis and sarcoma Kaposi.
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
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
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
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: 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: 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: chemistry; pharmacology.
SUBSTANCE: present invention refers to bioactive compounds of formula (Ic) , pharmaceutical compositions and application at cancer treatment, where R2-R7, X2, R, Q, G, J, L and M represent values estimated in invention formula and description.
EFFECT: production of compounds which can be used for anticancer medical product.
55 cl, 19 ex