Methods of inhibiting CXC intercrine molecules

• US 5,965,536 A
• Filed: 06/14/1996
• Issued: 10/12/1999
• Est. Priority Date: 12/15/1993
• Status: Expired due to Fees

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Hayashi, Shinichiro, Kurdowska, Anna K., Cohen, deceased, Allen Barry, Tuttle, Ronald R., Miller, Edmund J.
• Primary Examiner(s): DAVENPORT, AVIS MICHELLE
• Application Number:
  US08/666,564
• Time in Patent Office: 1,215 Days
• Field of Search: 514/13, 514/14, 514/15, 514/16, 514/17, 530/326, 530/327, 530/328, 530/329
• US Class Current: 514/21.8
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 14/54 Interleukins [IL]
• CPC Class Codes: C07K 14/5421 IL-8
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids

Abstract

Disclosed are methods for inhibiting and modulating the actions of CXC intercrine molecules. The antileukinate peptides described inhibit IL-8, GRO and MIP2β binding to neutrophils and neutrophil activation. The peptides are particularly advantageous as they inhibit IL-8-induced enzyme release at a 25 fold lower concentration than is required to inhibit chemotaxis, which makes them ideal for treating various inflammatory diseases and disorders including, amongst others, Adult Respiratory Distress Syndrome (ARDS), cystic fibrosis and chronic bronchitis.

Claims

1. A method of inhibiting a CXC intercrine family molecule, comprising contacting the CXC intercrine molecule or intercrine target cells with a biologically effective amount of a composition comprising a peptide of from 6 to about 14 residues in length including the amino acid sequence Arg Arg Trp Trp Cys Xaa₁ (SEQ ID NO:

23), wherein Xaa₁ is any amino acid residue.

2. The method of claim 1, wherein the CXC intercrine family molecule is IL-8.

3. The method of claim 1, wherein the CXC intercrine family molecule is GRO.

4. The method of claim 1, wherein the CXC intercrine family molecule is MIP2β

.

5. The method of claim 1, wherein the composition comprises an acylated peptide.

6. The method of claim 5, wherein the composition comprises a peptide acylated at the N-terminus.

7. The method of claim 1, wherein the composition comprises a peptide amidated at the C-terminus.

8. The method of claim 1, wherein the composition comprises a peptide acetylated at the N-terminus and amidated at the C-terminus.

9. The method of claim 1, wherein the composition comprises a peptide of D-amino acids.

10. The method of claim 1, wherein the composition comprises a peptide of L-amino acids.

11. The method of claim 1, wherein the composition comprises a peptide of L-amino acids and a peptide of D-amino acids.

12. The method of claim 1, wherein the composition comprises a peptide including both L-amino acids and D-amino acids.

13. The method of claim 1, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Arg (SEQ ID NO:

1).

14. The method of claim 1, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Ala (SEQ ID NO:

24).

15. The method of claim 1, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Cys (SEQ ID NO:

25).

16. The method of claim 1, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Asp (SEQ ID NO:

26).

17. The method of claim 1, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Glu (SEQ ID NO:

27).

18. The method of claim 1, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Phe (SEQ ID NO:

28).

19. The method of claim 1, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Gly (SEQ ID NO:

29).

20. The method of claim 1, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys His (SEQ ID NO:

30).

21. The method of claim 1, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Ile (SEQ ID NO:

31).

22. The method of claim 1, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Lys (SEQ ID NO:

32).

23. The method of claim 1, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Leu (SEQ ID NO:

33).

24. The method of claim 1, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Met (SEQ ID NO:

34).

25. The method of claim 1, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Asn (SEQ ID NO:

35).

26. The method of claim 1, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Pro (SEQ ID NO:

36).

27. The method of claim 1, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Gln (SEQ ID NO:

37).

28. The method of claim 1, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Ser (SEQ ID NO:

38).

29. The method of claim 1, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Thr (SEQ ID NO:

39).

30. The method of claim 1 wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Val (SEQ ID NO:

40).

31. The method of claim 1, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Trp (SEQ ID NO:

41).

32. The method of claim 1, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Tyr (SEQ ID NO:

42).

33. The method of claim 1, wherein the composition comprises a peptide including the amino acid sequence Arg Arg Trp Trp Cys Arg Xaa₂ (SEQ ID NO:

2), wherein Xaa₂ is any amino acid residue.

34. The method of claim 33, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Arg Ala (SEQ ID NO:

3).

35. The method of claim 33, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Arg Cys (SEQ ID NO:

4).

36. The method of claim 33, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Arg Asp (SEQ ID NO:

5).

37. The method of claim 33, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Arg Glu (SEQ ID NO:

6).

38. The method of claim 33, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Arg Phe (SEQ ID NO:

7).

39. The method of claim 33, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Arg Gly (SEQ ID NO:

8).

40. The method of claim 33, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Arg His (SEQ ID NO:

9).

41. The method of claim 33, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Arg Ile (SEQ ID NO:

10).

42. The method of claim 33, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Arg Lys (SEQ ID NO:

11).

43. The method of claim 33, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Arg Leu (SEQ ID NO:

12).

44. The method of claim 33, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Arg Met (SEQ ID NO:

13).

45. The method of claim 33, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Arg Asn (SEQ ID NO:

14).

46. The method of claim 33, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Arg Pro (SEQ ID NO:

15).

47. The method of claim 33, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Arg Gln (SEQ ID NO:

16).

48. The method of claim 33, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Arg Arg (SEQ ID NO:

17).

49. The method of claim 33, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Arg Ser (SEQ ID NO:

18).

50. The method of claim 33, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Arg Thr (SEQ ID NO:

19).

51. The method of claim 33, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Arg Val (SEQ ID NO:

20).

52. The method of claim 33, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Arg Trp (SEQ ID NO:

21).

53. The method of claim 33, wherein the composition comprises a peptide having the amino acid sequence Arg Arg Trp Trp Cys Arg Tyr (SEQ ID NO:

22).

54. The method of claim 1, wherein the composition further comprises a peptide having the amino acid sequence Gln Ile Pro Arg Arg Ser Trp Cys Arg Phe Leu Phe (SEQ ID NO:

52).

55. The method of claim 1, wherein the composition is a pharmaceutical composition in a pharmacologically acceptable form.

56. The method of claim 55, wherein the pharmaceutical composition is formulated as an injectable, a nasal spray, an inhalant, an aerosol, a cream, a gel, a micelle or liposome encapsulated form or is incorporated within a biocompatible drug release capsule.

57. The method of claim 56, wherein the pharmaceutical composition is formulated as an injectable for intravenous, intramuscular or subcutaneous administration.

58. The method of claim 56, wherein the pharmaceutical composition is formulated as a nasal spray, an inhalant or an aerosol.

59. The method of claim 55, wherein the CXC intercrine family molecule or the intercrine target cells are located within an animal and an effective amount of the pharmaceutical composition is administered to said animal.