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Details for Patent: 6,228,983

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Details for Patent: 6,228,983

Title: Human respiratory syncytial virus peptides with antifusogenic and antiviral activities
Abstract:The present invention relates to peptides which exhibit antifusogenic and antiviral activities. The peptides of the invention consist of a 16 to 39 amino acid region of a human respiratory syncytial virus protein. These regions were identified through computer algorithms capable of recognizing the ALLMOTI5, 107x178x4, or PLZIP amino acid motifs. These motifs are associated with the antifusogenic and antiviral activities of the claimed peptides.
Inventor(s): Barney; Shawn O'Lin (Cary, NC), Lambert; Dennis Michael (Cary, NC), Petteway; Stephen Robert (Cary, NC)
Assignee: Trimeris, Inc. (Durham, NC)
Filing Date:Jun 07, 1995
Application Number:08/485,264
Claims:1. An isolated peptide consisting of an amino acid sequence of a 16 to 39 amino acid region of a human respiratory syncytial virus protein, wherein said region is identified by an ALLMOTI5, 107x178x4, or PLZIP sequence search motif, said peptide further consisting of an amino terminal X, and a carboxy terminal Z in which:

X comprises an amino group, an acetyl group, a 9-fluorenylmethoxy-carbonyl group, a hydrophobic group, or a macromolecular carrier group; and

Z comprises a carboxyl group, an amido group, a hydrophobic group, or a macromolecular carrier group.

2. A peptide having the formula: ##STR6##

in which:

amino acid residues are presented by the single-letter code;

X comprises an amino group, an acetyl group, a 9-fluorenylmethoxy-carbonyl group, a hydrophobic group, or a macromolecular carrier group;

Z comprises a carboxyl group, an amido group, a hydrophobic group, or a macromolecular carrier group for an effective period of time so that no infection of the cell by the virus occurs.

3. The peptide of claim 1 or 2 wherein X is a hydrophobic group.

4. The peptide of claim 3 wherein the hydrophobic group X is carbobenzoxyl, dansyl, or t-butyloxycarbonyl.

5. The peptide of claim 1 or 2 wherein Z is a hydrophobic group.

6. The peptide of claim 5 wherein the hydrophobic group Z is t-butyloxycarbonyl.

7. The peptide of claim 1 or 2 wherein X is a macromolecular carrier group.

8. The peptide of claim 7 wherein the macromolecular carrier group is a lipid-fatty acid conjugate, a polyethylene glycol, or a carbohydrate moiety.

9. The peptide of claim 1 or 2 wherein Z is a macromolecular carrier group.

10. The peptide of claim 9 wherein the macromolecular carrier group Z is a lipid-fatty acid conjugate, a polyethylene glycol, or a carbohydrate moiety.

11. The peptide of claim 2 wherein at least one bond linking adjacent amino acid residues is a non-peptide bond.

12. The peptide of claim 11 wherein the non-peptide bond is an imino, ester, hydrazine, semicarbazide, or azo bond.

13. The peptide of claim 2 wherein at least one amino acid residue is in a D-isomer configuration.

14. The peptide of claim 2, wherein the peptide has the formula:

X-TSVITIELSNIKENKCNGTDAKVKLIKQELDKYKN-Z (SEQ ID NO. 125).

15. The peptide of claim 2, wherein the peptide has the formula:

X-SVITIELSNIKENKCNGTDAKVKLIKQELDKYKNA-Z (SEQ ID NO. 126).

16. The peptide of claim 2, wherein the peptide has the formula:

X-VITIELSNIKENKCNGTDAKVKLIKQELDKYKNAV-Z (SEQ ID NO. 210).

17. The peptide of claim 2, wherein the peptide has the formula:

X-VAVSKVLHLEGEVNKIALLSTNKAVVSLSNGVS-Z (SEQ ID NO. 20).

18. The peptide of claim 2, wherein the peptide has the formula:

X-AVSKVLHLEGEVNKIALLSTNKAVVSLSNGVSV-Z (SEQ ID NO. 21).

19. The peptide of claim 2, wherein the peptide has the formula:

X-VSKVLHLEGEVNKIALLSTNKAVVSLSNGVSVL-Z (SEQ ID NO. 22).

20. The peptide of claim 2, wherein the peptide has the formula:

X-SKVLHLEGEVNKIALLSTNKAVVSLSNGVSVLT-Z (SEQ ID NO. 23).

21. The peptide of claim 2, wherein the peptide has the formula:

X-KVLHLEGEVNKIALLSTNKAVVSLSNGVSVLTS-Z (SEQ ID NO. 24).

22. The peptide of claim 2, wherein the peptide has the formula:

X-LEGEVNKIALLSTNKAVVSLSNGVSVLTSKVLD-Z (SEQ ID NO. 25).

23. The peptide of claim 2, wherein the peptide has the formula:

X-GEVNKIALLSTNKAVVSLSNGVSVLTSKVLDLK-Z (SEQ ID NO. 26).

24. The peptide of claim 2, wherein the peptide has the formula:

X-EVNKIALLSTNKAVVSLSNGVSVLTSKVLDLKN-Z (SEQ ID NO. 27).

25. The peptide of claim 2, wherein the peptide has the formula:

X-VNKIALLSTNKAVVSLSNGVSVLTSKVLDLKNY-Z (SEQ ID NO. 28).

26. The peptide of claim 2, wherein the peptide has the formula:

X-NKIALLSTNKAVVSLSNGVSVLTSKVLDLKNYI-Z (SEQ ID NO. 29).

27. The peptide of claim 2, wherein the peptide has the formula:

X-KIALLSTNKAVVSLSNGVSVLTSKVLDLKNYID-Z (SEQ ID NO. 30).

28. The peptide of claim 2, wherein the peptide has the formula:

X-IALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK-Z (SEQ ID NO. 31).

29. The peptide of claim 2, wherein the peptide has the formula:

X-ALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDKQ-Z (SEQ ID NO. 32).

30. The peptide of claim 2, wherein the peptide has the formula:

X-DEFDASISQVNEKINQSLAFIRKSDELL-Z (SEQ ID NO. 211).

31. The peptide of claim 2, wherein the peptide has the formula:

X-IINFYDPLVFPSDEFDASISQVNEKINQSLAFIRK-Z (SEQ ID NO. 212).

32. The peptide of claim 2, wherein the peptide has the formula:

X-INFYDPLVFPSDEFDASISQVNEKINQSLAFIRKS-Z (SEQ ID NO. 213).

33. The peptide of claim 2, wherein the peptide has the formula:

X-FYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDE-Z (SEQ ID NO. 214).

34. The peptide of claim 2, wherein the peptide has the formula:

X-YDPLVFPSDEFDASISQVNEKINQSLAFIRKSDEL-Z (SEQ ID NO. 215).

35. The peptide of claim 2, wherein the peptide has the formula:

X-DPLVFPSDEFDASISQVNEKINQSLAFIRKSDELL-Z (SEQ ID NO. 216).

36. The peptide of claim 2, wherein the peptide has the formula:

X-PLVFPSDEFDASISQVNEKINQSLAFIRKSDELLH-Z (SEQ ID NO. 217).

37. The peptide of claim 2, wherein the peptide has the formula:

X-LVFPSDEFDASISQVNEKINQSLAFIRKSDELLHN-Z (SEQ ID NO. 218).

38. The peptide of claim 2, wherein the peptide has the formula:

X-VFPSDEFDASISQVNEKINQSLAFIRKSDELLHNV-Z (SEQ ID NO. 219).

39. The peptide of claim 2, wherein the peptide has the formula:

X-FPSDEFDASISQVNEKINQSLAFIRKSDELLHNVN-Z (SEQ ID NO. 220).

40. The peptide of claim 2, wherein the peptide has the formula:

X-PSDEFDASISQVNEKINQSLAFIRKSDELLHNVNA-Z (SEQ ID NO. 221).

41. The peptide of claim 2, wherein the peptide has the formula:

X-SDEFDASISQVNEKINQSLAFIRKSDELLHNVNAG-Z (SEQ ID NO. 222).

42. The peptide of claim 2, wherein the peptide has the formula:

X-DEFDASISQVNEKINQSLAFIRKSDELLHNVNAGK-Z (SEQ ID NO. 223).

43. The peptide of claim 2, wherein the peptide has the formula:

X-EFDASISQVNEKINQSLAFIRKSDELLHNVNAGKS-Z (SEQ ID NO. 224).

44. The peptide of claim 2, wherein the peptide has the formula:

X-FDASISQVNEKINQSLAFIRKSDELLHNVNAGKST-Z (SEQ ID NO. 225).

45. The peptide of claim 2, wherein the peptide has the formula:

X-DASISQVNEKINQSLAFIRKSDELLHNVNAGKSTT-Z (SEQ ID NO. 226).

46. The peptide of claim 2, wherein the peptide has the formula:

X-FDASISQVNEKINQSLAFIRKSDELLHNVNAGK-Z (SEQ ID NO. 143).

47. The peptide of claim 2, wherein the peptide has the formula:

X-FDASISQVNEKINQSLAFIRKSDELLHNVNA-Z (SEQ ID NO. 227).

48. The peptide of claim 2, wherein the peptide has the formula:

X-FDASISQVNEKINQSLAFIRKSDELLHNV-Z (SEQ ID NO. 228).

49. The peptide of claim 2, wherein the peptide has the formula:

X-FDASISQVNEKINQSLAFIRKSDELLH-Z (SEQ ID NO. 229).

50. The peptide of claim 2, wherein the peptide has the formula:

X-FDASISQVNEKINQSLAFIRKSDEL-Z (SEQ ID NO. 230).

51. The peptide of claim 2, wherein the peptide has the formula:

X-ASISQVNEKINQSLAFIRKSDELLHNVNAGKST-Z (SEQ ID NO. 144).

52. The peptide of claim 2, wherein the peptide has the formula:

X-ISQVNEKINQSLAFIRKSDELLHNVNAGKST-Z (SEQ ID NO. 231).

53. The peptide of claim 2, wherein the peptide has the formula:

X-QVNEKINQSLAFIRKSDELLHNVNAGKST-Z (SEQ ID NO. 232).

54. The peptide of claim 1, wherein the region of the human respiratory syncytial virus protein consists of a region of 28 amino acid residues identified by the ALLMOTI5 sequence search motif.

55. The peptide of claim 1, wherein the region of the human respiratory syncytial virus protein consists of a region of 35 amino acid residues identified by the ALLMOTI5 sequence search motif.

56. The peptide of claim 1, wherein the region of the human respiratory syncytial virus protein is consists of a region of 28 amino acid residues identified by the 107x178x4 sequence search motif.

57. The peptide of claim 1, wherein the region of the human respiratory syncytial virus protein consists of a region of 35 amino acid residues identified by the 107x178x4 sequence search motif.

58. The peptide of claim 1, wherein the region of the human respiratory syncytial virus protein is identified by the PLZIP sequence search motif.

59. The peptide of claim 7, wherein the macromolecular group is a peptide group.

60. The peptide of claim 59, wherein the peptide group is about 2 to about 50 amino acid residues amino to the region of the human respiratory syncytial virus protein identified by the ALLMOTI5, 107x178x4, or PLZIP sequence search motif.

61. The peptide of claim 9, wherein the macromolecular group is a peptide group.

62. The peptide of claim 61, wherein the peptide group is about 2 to about 50 amino acid residues amino to the region of the human respiratory syncytial virus protein identified by the ALLMOTI5, 107x178x4, or PLZIP sequence search motif.
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