A polypeptide with il-10 similar properties (options), the conjugate of the polypeptide, pharmaceutical composition, method of modulating an immune response in a mammal

 

The invention relates to biotechnology and can be used to obtain a polypeptide with IL-10 similar properties. The polypeptide contains no more than 100 amino acids and includes the sequence Thr-X4-Lys-X5-Arg-X6where X4and X5can be Met, Ile, Leu, Val and X6may be Asn, Asp, Gln, Glu. The polypeptide has at least one of the following properties: induces suppression of IL-8 induces the suppression of IL-1induces the formation of human monocytes protein, induces chemotactic migration of CD8+-T-lymphocytes, desensibilisation CD8+T cells, suppresses the chemotactic response of human monocytes, does not suppress the expression of molecules of MHC class II on monocytes, induces the formation of IL-4, lower education-TNF. Pharmaceutical composition for modulating the immune response in a mammal contains a polypeptide with IL-10 similar properties. The invention allows the development of tools for the treatment of diseases, pathogenesis of which is associated with a change in the function of mediators immunomodulary. 11 C. and 29 C.p. f-crystals, 13 ill. 4 table.

Description text in facsimile form (see graphic part)more 100 amino acid residues, which includes the following sequence:

Thr-X4-Lys-X5-Arg-X6(SEQ ID no: 19),

where X4and X5independently selected from the group consisting of Met, Ile, Leu and Vl;

X6selected from the group consisting of Asn, Asp, Gln and Glu,

and which has at least one of the following properties: (a) induces inhibition of the spontaneous production of IL-8 by human monocytes, b) induces inhibition of IL-1-induced production of IL-8 by mononuclear cells of peripheral blood (RVMS)) induces the production of protein-receptor antagonist interleukin-1 (IRAP) by human monocytes, g) induces in vitro chemotactic migration of CD8+-T-lymphocytes person, d) desensibilisation CD8+-T-cells, leading to areactively in respect of rhIL-10, e) causes suppression of chemotactic response of CD4+-T-human lymphocytes to IL-8, W) causes the suppression of chemotactic response of human monocytes to MCAF/MCP-1, C) induces the production of IL-4 cultured CD4+-T-cells of healthy people, and reduces the production of TNFin the reaction of mixed leukocytes of man.

2. A polypeptide with IL-10-like properties under item 1, characterized in that it includes the , X4and X5independently selected from the group consisting of Met, He, Leu and Val;

X6selected from the group consisting of Asn, Asp, Gln and Glu.

3. A polypeptide with IL-10-like properties under item 1, characterized in that it contains the following sequence:

X2-X3-Thr-X4-Lys-X5-Arg-X6(SEQ ID no:21),

where X2is a Tight or Phe,

X3, X4and X5independently selected from the group consisting of Met, Ile, Leu and Val; and

X6selected from the group consisting of Asn, Asp, Gin and Glu.

4. A polypeptide with IL-10-like properties under item 1, characterized in that it comprises the following sequence:

X1-X2-X3-Thr-X4-Lys-X5-Arg-X6(SEQ ID no:22),

where X1represents Ala or Gly;

X2is a Tight or Phe;

X3, X4and X5independently selected from the group consisting of Met, He, Leu and Val;

X6selected from the group consisting of Asn, Asp, Gln and Glu.

5. A polypeptide with IL-10-like properties according to any one of paragraphs.1-4, containing at least 12 amino acids.

6. A polypeptide with IL-10-like properties according to any one of paragraphs.1-4, containing at least 15 amino acids.

7. A polypeptide with IL-10-like properties according to any one of paragraphs.1-4, sod is s at least 10 amino acids.

9. A polypeptide with IL-10-like properties, those having the formula:

X1-X2-X3-Thr-X4-Lys-X5-Arg-X6(SEQ ID no: 22),

where X1represents Ala or Gly;

X2is a Tight or Phe;

X3, X4and X5independently selected from the group consisting of Met, Ile, Leu and Val;

X6selected from the group consisting of Asn, Asp, Gln and Glu.

10. The polypeptide according to any one of paragraphs.4-9, characterized in that X1represents Ala.

11. A polypeptide with IL-10-like properties, those having the formula:

X2-X3-Thr-X4-Lys-X5-Arg-X6(SEQ ID no:21),

where X2is a Tight or Phe;

X3, X4and X5independently selected from the group consisting of Met, Ile, Leu and Val;

X6selected from the group consisting of Asn, Asp, Gln and Glu.

12. The polypeptide according to any one of paragraphs.4-9 or 11, characterized in that X1represents Gly.

13. A polypeptide with IL-10-like properties, those having the formula:

X3-Thr-X4-Lys-X5-Arg-X6(SEQ ID no: 20),

where X3, X4and X5independently selected from the group consisting of Met, Ile, Leu and Val;

X6selected from the group consisting of Asn, Asp, Gln and Glu.

14. A polypeptide with IL-10-like properties, those having the formula:

she Met, Ile, Leu and Val;

X6selected from the group consisting of Asn, Asp, Gln and Glu.

15. The polypeptide according to any one of paragraphs.3-9 or 10-12, wherein X2is a Tight.

16. The polypeptide according to any one of paragraphs.3-9 or 10-12, wherein X2represents Phe.

17. The polypeptide according to any one of paragraphs.2-14, 15 or 16, characterized in that X3represents Met.

18. The polypeptide according to any one of paragraphs.2-14, 15 or 16, characterized in that X3represents Il.

19. The polypeptide according to any one of paragraphs.2-14, 15 or 16, characterized in that X3represents Leu.

20. The polypeptide according to any one of paragraphs.2-14, 15 or 16, characterized in that X3represents Val.

21. The polypeptide according to any one of paragraphs.1-20, characterized in, read the X4represents Met.

22. The polypeptide according to any one of paragraphs.1-20, characterized in that X4represents Il.

23. The polypeptide according to any one of paragraphs.1-20, characterized in that X4represents Leu.

24. The polypeptide according to any one of paragraphs.1-20, characterized in that X4represents Val.

25. The polypeptide according to any one of paragraphs.1-24, characterized in that X5represents Met.

26. The polypeptide according to any one of paragraphs.1-24, characterized in that X5represents Il.

27. Polyp.1-24, characterized in that X5represents Val.

29. The polypeptide according to any one of paragraphs.1-28, wherein X6is an Asp.

30. The polypeptide according to any one of paragraphs.1-28, wherein X6represents Gln.

31. The polypeptide according to any one of paragraphs.1-28, wherein X6represents Glu.

32. The polypeptide according to any one of paragraphs.1-28, wherein X6represents Asn.

33. A polypeptide with IL-10-like properties, having the amino acid sequence Ala-Tyr-Met-Thr-Met-Lys-Ile-Arg-Asn (SEQ ID no:1).

34. A polypeptide with IL-10-like properties selected from the group consisting of

Ala-Tyr-Met-Thr-Il-Lys-Met-Arg-Asn (SEQ ID no:2),

Ala-Phe-Met-Thr-Leu-Lys-Leu-Arg-Asn (SEQ ID no:3),

Ala-Tyr-Met-Thr-Met-Lys-Val-Arg-Glu (SEQ ID no:4),

Glu-Tyr-Met-Thr-Met-Lys-Ile-Arg-Asp (SEQ ID no:5),

Ala-Phe-Met-Thr-Met-Lys-Ile-Arg-Asp (SEQ ID no:6),

Ala-Tyr-Ile-Thr-Met-Lys-Ile-Arg-Asp (SEQ ID no:7),

Ala-Tyr-Leu-Thr-Met-Lys-Ile-Arg-Asp (SEQ ID no:8),

Ala-Tyr-Val-Thr-Met-Lys-Ile-Arg-Asp (SEQ ID no:9),

Ala-Tyr-Met-Thr-Ile-Lys-Ile-Arg-Asp (SEQ ID no:10),

Ala-Tyr-Met-Thr-Leu-Lys-Ile-Arg-Asp (SEQ ID no:11),

Ala-Tyr-Met-Thr-Val-Lys-Ile-Arg-Asp (SEQ ID no:12),

Ala-Tyr-Met-Thr-Met-Lys-Ile-Arg-Asp (SEQ ID no:13),

Ala-Tyr-Met-Thr-Met-Lys-Met-Arg-Asp (SEQ ID no:14),

Ala-Tyr-Met-Thr-Met-Lys-Val-Arg-Asp (SEQ ID no:15),

Ala-Tyr-Met-Thr-Met-Lys-Ile-Arg-Gln (SEQ ID no:16) and

Ala-Tyr-Met-Thr-Met-Lys-Ile-Arg-Glu (SEQ ID no:17).

35. The conjugate of the polypeptide with IL-10-like properties, soderjanie properties according to any one of paragraphs.1, 9, 11, 13, 14, and 33 or conjugate of the polypeptide by p. 35, characterized in that it has at least one of the properties (a)-(I) specified in paragraph 1.

37. The polypeptide or conjugate according to any one of paragraphs.1-36 in substantially pure form.

38. Pharmaceutical composition for modulating the immune response in a mammal containing polypeptide with IL-10-like properties according to any one of paragraphs.1, 9, 11, 13, 14 and 33 or conjugate of the polypeptide with IL-10-like properties p. 35 in an effective amount.

39. A polypeptide with IL-10-like properties, representing a polypeptide with IL-10-like properties according to any one of paragraphs.1, 9, 11, 13, 14 and 33 or conjugate of the polypeptide with IL-10-like properties p. 35, to modulate an immune response in a mammal in the treatment or prevention of a disease selected from the group consisting of premature birth, infection, or other conditions, rheumatoid arthritis, arthritis Lima, gout, septic syndrome, hyperthermia, ulcerative colitis or enterocolitis, osteoporosis, cytomegalovirus, periodontal disease, glomerulonephritis, chronic non-infectious inflammation of the lung (for example, sarcoidosis and light smoker), granuloma formation, fibrosis of the liver, fibrosis easy, the strictly myeloid leukemia and other neoplastic diseases, bronchial asthma, diabetes mellitus type 1 (insulin-dependent), arteriosclerosis/atherosclerosis, psoriasis, chronic lymphocytic leukemia, common variable immune deficiency, side effects of other biological response modifiers, disseminated intravascular coagulation, systemic sclerosis, encephalomyelitis, pneumonia, syndrome, Hyper-IgE-globulinemia, enterocolitis, cancer metastasis and growth of the adaptive immune therapy, acquired respiratory distress syndrome, sepsis, reperfusion syndrome, surgical inflammation, organ transplantation, and alopecia.

40. A method of modulating an immune response in a mammal in the treatment and/or prevention of a disease selected from the group consisting of premature birth, infection, or other conditions, rheumatoid arthritis, arthritis Lima, gout, septic syndrome, hyperthermia, ulcerative colitis or enterocolitis, osteoporosis, cytomegalovirus, periodontal disease, glomerulonephritis, chronic non-infectious inflammation of the lung (e.g., sarcoidosis, and light is transplantat vs. host chronic myeloid leukemia, acute myeloid leukemia and other neoplastic diseases, bronchial asthma, diabetes mellitus type 1 (insulin-dependent), arteriosclerosis/atherosclerosis, psoriasis, chronic lymphocytic leukemia, common variable immune deficiency, side effects of other biological response modifiers, disseminated intravascular coagulation, systemic sclerosis, encephalomyelitis, pneumonia syndrome Hyper-IgE-globulinemia, enterocolitis, cancer metastasis and growth of the adaptive immune therapy, acquired respiratory distress syndrome, sepsis, reperfusion syndrome, surgical inflammation, organ transplantation, and alopecia, includes introduction to the mammal a therapeutically or prophylactically effective amount of the polypeptide with IL-10-like properties of PP.1, 9, 11, 13, 14 and 33 or conjugate of the polypeptide with IL-10-like properties p. 35.

 

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