Peyer's patch and/or M-cell targeting ligands

1. A purified synthetic polypeptide ligand comprising a 12-mer L-peptide or homologue thereof, said 12-mer L-peptide selected from the group consisting of SEQ ID NO:25 and SEQ ID NOs:38-39 wherein said homologue is at least 9/12 homologous to a 12-mer peptide selected from said group and wherein said 12-mer L-peptide or homologue thereof, when integrated as an N-terminal PIII fusion peptide of an M13 phage confers an ability to bind the phage to either Caco-2 cell, IEC-6 cell, rat, mouse, pig or dog homogenate membrane fractions, said ability being at least as great as that conferred by a similarly integrated 12-mer peptide of SEQ ID NO:67, wherein said ligand comprises a zinc-binding domain.

2. A purified synthetic polypeptide ligand comprising a 12-mer L-peptide or homologue thereof, said 12-mer L-peptide selected from the group consisting of SEQ ID NO:25 and SEQ ID NOs:38-39 wherein said homologue is at least 9/12 homologous to a 12-mer peptide selected from said group and wherein said 12-mer L-peptide or homologue thereof, when integrated as an N-terminal PIII fusion peptide of an M13 phage confers an ability to bind the phage to either Caco-2 cell, IEC-6 cell, rat, mouse, pig or dog homogenate membrane fractions, said ability being at least as great as that conferred by a similarly integrated 12-mer peptide of SEQ ID NO:67, wherein said ligand comprises a 12-mer L-peptide selected from the group consisting of SEQ ID NO:25 and SEQ ID NOs:38-39.

3. A purified synthetic polypeptide ligand comprising a 12-mer L-peptide or homologue thereof, said 12-mer L-peptide selected from the group consisting of SEQ ID NO:25 and SEQ ID NOs:38-39 wherein said homologue is at least 9/12homologous to a 12-mer peptide selected from said group and wherein said 12-mer L-peptide or homologue thereof, when integrated as an N-terminal PIII fusion peptide of an M13 phage confers an ability to bind the phage to either Caco-2 cell, IEC-6 cell, rat, mouse, pig or dog homogenate membrane fractions, said ability being at least as great as that conferred by a similarly integrated 12-mer peptide of SEQ ID NO:67, wherein said polypeptide ligand is at least 30 amino acids in length.

4. A purified synthetic polypeptide ligand comprising a 12-mer D-peptide, or homologue thereof, said 12-mer L-peptide selected from the group consisting of D-forms of 12-mer L-peptides of SEQ ID NO:25 SEQ ID NOs:38-39 and wherein said homologue is at least 9/12 homologous to a 12-mer D-peptide selected from said group and wherein said 12-mer D-peptide or homologue, when integrated as an N-terminal PIII fusion peptide of an M13 phage confers an ability to bind the phage to either Caco-2 cell, IEC-6 cell, rat, mouse, pig or dog homogenate membrane fractions, said ability being at least as great as that conferred by a similarly integrated 12-mer peptide of SEQ ID NO:67.

5. A purified synthetic polypeptide ligand of claim 4 , wherein said ligand comprises a zinc-binding domain.

6. A purified synthetic polypeptide ligand of claim 4 , wherein the homologue is at least 10/12 homologous to a 12-mer D-peptide.

7. A purified synthetic polypeptide ligand of claim 4 , wherein the homologue is at least 11/12 homologous to a 12-mer D-peptide.

8. A purified synthetic polypeptide ligand of claim 4 , wherein said ligand comprises a 12-mer D-peptide being the D-form of a 12-mer L-peptide selected from the group consisting of SEQ ID NO:25 and SEQ ID NOs:38-39.

9. A purified synthetic polypeptide ligand of claim 4 , wherein said D-peptide is selected from the group consisting of SEQ ID NO:37 corresponding to the D-form of 12-mer L-peptide of SEQ ID NO:25.

10. A purified synthetic polypeptide ligand of claim 4 , wherein said ligand consists of the D-form of an amino acid sequence selected from the group consisting of SEQ ID NO:25 and SEQ ID NOs:38-39 or homologue thereof.

11. The purified synthetic polypeptide ligand of claim 4 , wherein said ligand consists of the D-form of a 12-mer L-peptide selected from the group consisting of SEQ ID NO:25 and SEQ ID NOs:38-39.

12. A purified synthetic polypeptide ligand of claim 4 , wherein the homologue is at least 10/12 homologous.

13. A purified synthetic polypeptide ligand of claim 4 , wherein the homologue is at least 11/12 homologous.

14. A purified synthetic polypeptide ligand of claim 4 , wherein said ligand is at most 200 amino acids in length.

15. A purified synthetic polypeptide ligand of claim 4 , wherein said ligand is at least 12 amino acids in length.

16. A purified synthetic polypeptide ligand of claim 4 , wherein said polypeptide ligand is at least 30 amino acids in length.

17. A purified synthetic polypeptide ligand of claim 4 , wherein said 12-mer L-peptide is VPPHPMTYSCQY (SEQ ID NO:25).

18. A purified synthetic polypeptide ligand comprising a 12-mer retro-inverted peptide or homologue thereof, said 12-mer retro-inverted peptide being the retro-inverted form of a 12-mer L-peptide selected from the group consisting of retro-inverted forms of 12-mer L-peptides of SEQ ID NO:25 and SEQ ID NOs:38-39, wherein said homologue is at least 9/12 homologous to a 12-mer retro-inverted peptide selected from said group and wherein said 12-mer retro-inverted peptide or homologue, when integrated as an N-terminal PIII fusion peptide of an M13 phage confers an ability to bind the phage to either Caco-2 cell, IEC-6 cell, rat, mouse, pig or dog homogenate membrane fractions, said ability being at least as great as that conferred by a similarly integrated 12-mer peptide of SEQ ID NO:67.

19. A purified synthetic polypeptide ligand of claim 18 , wherein said ligand comprises a zinc-binding domain.

20. A purified synthetic polypeptide ligand of claim 18 , wherein the homologue is at least 10/12 homologous to a 12-mer retro-inverted peptide.

21. A purified synthetic polypeptide ligand of claim 18 , wherein the homologue is at least 11/12 homologous to a 12-mer retro-inverted peptide.

22. A purified synthetic polypeptide ligand of claim 18 , wherein said ligand comprises a 12-mer retro-inverted peptide being the retro-inverted form of a 12-mer L-peptide selected from the group consisting of SEQ ID NO:25 and SEQ ID NOs:38-39.

23. A purified synthetic polypeptide ligand of claim 18 , wherein said ligand consists only of a retro-inverted form of a 12-mer L-peptide of an amino acid sequence selected from the group consisting of SEQ ID NO:25 and SEQ ID NOs:38-39 or homologue thereof.

24. A purified synthetic polypeptide ligand of claim 18 , wherein said ligand consists of the retro-inverted form of a 12-mer L-peptide selected from the group consisting of SEQ ID NO:25 and SEQ ID NOs:38-39.

25. A purified synthetic polypeptide ligand of claim 18 , wherein said retro-inverted peptide is SEQ ID NO:40 corresponding to the retro-inverted form of 12-mer L-peptide SEQ ID NO:25.

26. A purified synthetic polypeptide ligand of claim 18 , wherein the homologue is at least 10/12 homologous to a 12-mer peptide.

27. A purified synthetic polypeptide ligand of claim 18 , wherein said ligand is at most 200 amino acids in length.

28. A purified synthetic polypeptide ligand of claim 18 , wherein said ligand is at least 12 amino acids in length.

29. The purified synthetic polypeptide ligand of claim 18 , wherein said polypeptide ligand is at least 30 amino acids in length.

30. A purified synthetic polypeptide ligand of claim 18 , wherein the 12-mer L-peptide is VPPHPMTYSCQY (SEQ ID NO:25).

31. A purified synthetic polypeptide ligand of claim 4 , or 18 , wherein said polypeptide ligand is integrated into the protein of a phage.

32. The ligand of claim 31 , wherein said polypeptide ligand is expressed on the surface of a phage further comprising an antigen and/or a gene encoding the antigen also expressed on the surface.

33. The ligand of claim 31 , wherein said polypeptide ligand is expressed on the surface of a bacterium further comprising an antigen and/or a gene encoding the antigen also expressed on the surface.

34. A purified synthetic polypeptide ligand of claim 4 , or 18 , wherein said polypeptide ligand is covalently or non-covalently bound to a carrier entity comprising a pharmaceutical agent.

35. The purified synthetic polypeptide ligand of claim 34 , wherein said carrier entity is selected from the group consisting of a nanoparticle, a microparticle, a liposome, a bacterium, a phage and a virus.

36. The purified synthetic polypeptide ligand of claim 35 , wherein said carrier entity is selected from the group consisting of a nanoparticle, microparticle and a liposome.

37. The purified synthetic polypeptide ligand of claim 36 , wherein said carrier entity has a largest dimension that is in the range of 10 nm to 500 .mu.m.

38. The ligand of claim 34 , wherein said pharmaceutical agent is a drug or therapeutic agent.

39. The ligand of claim 34 , wherein said pharmaceutical agent is a pathogen antigen.

40. The ligand of claim 34 , wherein said pharmaceutical agent is an adjuvant.

41. The purified synthetic polypeptide ligand of claim 34 , wherein said carrier entity is selected from the group consisting of a phage and a virus.

42. A method of administering a pharmaceutical agent to an organism having intestinal epithelium, said method comprising contacting said intestinal epithelium with said purified synthetic polypeptide ligand of claim 4 or 18 , said ligand being covalently, or non-covalently bound to, a carrier entity.

43. The method of claim 42 , wherein said organism is a mammal.

44. The method of claim 43 , wherein said mammal is a human.

45. The method of claim 42 , wherein said carrier entity is selected from the group consisting of a nanoparticle, microparticle liposome, bacterial, phage and a viral carrier.

46. The method of claim 42 , wherein said carrier entity is selected from the group consisting of a nanoparticle, microparticle and liposome.

47. The method of claim 46 , wherein said carrier entity has its major dimension in the range of 10 nm to 500 μm.

48. The method of claim 46 , wherein said nanoparticle, microparticle, or liposome is loaded with a pharmaceutical agent or encapsulated with a pharmaceutical agent.

49. The method of claim 42 , wherein said administration is done via the oral route.

50. The method of claim 42 wherein said administration is done via either a rectal, subcutaneous, intramuscular, nasal or intravenous route.

51. The method of claim 42 , wherein said pharmaceutical agent is a vaccine.

52. The method of claim 42 , wherein said purified synthetic polypeptide ligand is a peptide integrated into the protein of a phage which is coated, adsorbed or covalently bonded to a surface of a carrier that is either a nanoparticle or microparticle.

53. The method of claim 52 , wherein said phage is modified to contain DNA encoding an antigen.

54. The method of claim 52 , wherein said nanoparticle or microparticle is loaded with a pharmaceutical agent or encapsulated with a pharmaceutical agent.

55. A method of claim 42 , wherein the purified synthetic polypeptide ligand comprises a zinc-binding motif, and said ligand is contacted with said epithelium in the presence of zinc.

56. A method of claim 42 , wherein said carrier entity is selected from the group consisting of a phage and a viral carrier.

57. The method of claim 56 , wherein said phage comprises a targeting ligand on its surface.

58. A purified synthetic polypeptide ligand comprising a 12-mer L-peptide or homologue thereof, said 12-mer L-peptide selected from the group consisting of SEQ ID NO:25 ad SEQ ID NOs:38-39 wherein said homologue is at least 9/12 homologous to a 12-mer peptide selected from said group ad wherein said 12-mer L-peptide or homologue thereof, when integrated as an N-terminal PIII fusion peptide of a M13 phage confers an ability to bind the phage to either Caco-2 cell, IEC-6 cell, rat, mouse, pig or dog homogenate membrane fractions, said ability being at least as great as that conferred by a similarly integrated 12-mer peptide of SEQ ID NO:67, wherein said polypeptide ligand is integrated into the protein of a phage and wherein said polypeptide ligand is expressed on the surface of a phage further comprising an antigen and/or a gene encoding the antigen also expressed on the surface.

59. A purified synthetic polypeptide ligand comprising a 12-mer L-peptide or homologue thereof, said 12-mer L-peptide selected from the group consisting of SEQ ID NO:25 and SEQ ID NOs:38-39 wherein said homologue is at least 9/12 homologous to a 12-mer peptide selected from said group and wherein said 12-mer L-peptide or homologue thereof, when integrated as an N-terminal PIII fusion peptide of an M13 phage confers an ability to bind the phage to either Caco-2 cell, IEC-6 cell, rat, mouse, pig or dog homogenate membrane fractions, said ability being at least as great as that conferred by a similarly integrated 12-mer peptide of SEQ ID NO:67, wherein said polypeptide ligand is integrated into the protein of a phage and wherein said polypeptide ligand is expressed on the surface of a bacterium further comprising an antigen and/or a gene encoding the antigen also expressed on the surface.

60. A purified synthetic polypeptide ligand comprising a 12-mer L-peptide or homologue thereof, said 12-mer L-peptide selected from the group consisting of SEQ ID NO:25 and SEQ ID NOs:38-39 wherein said homologue is at least 9/12 homologous to a 12-mer peptide selected from said group and wherein said 12-mer L-peptide or homologue thereof, when integrated as an N-terminal PIII fusion peptide of an M13 phage confers an ability to bind the phage to either Caco-2 cell, IEC-6 cell, rat, mouse, pig or dog homogenate membrane fractions, said ability being at least as great as that conferred by a similarly integrated 12-mer peptide of SEQ ID NO:67, wherein said polypeptide ligand is covalently or non-covalently bound to a carrier entity comprising a pharmaceutical agent, wherein said pharmaceutical agent is an adjuvant.

61. A method of administering a pharmaceutical agent to an organism having intestinal epithelium, said method comprising contacting said intestinal epithelium with a purified synthetic polypeptide ligand comprising a 12-mer L-peptide or homologue thereof, said 12-mer L-peptide selected from the group consisting of SEQ ID NO:25 and SEQ ID NOs:38-39 wherein said homologue is at least 9/12 homologous to a 12-mer peptide selected from said group and wherein said 12-mer L-peptide or homologue thereof, when integrated as an N-terminal PIII fusion peptide of an M13 phage confers an ability to bind the phage to either Caco-2 cell. IEC-6 cell, rat, mouse, pig or dog homogenate membrane fractions, said ability being at least as great as that conferred by a similarly integrated 12-mer peptide of SEQ ID NO:67, said ligand being covalently, or non-covalently bound to, a carrier entity, wherein said administration is done via either a rectal, subcutaneous, intramuscular, nasal or intravenous route.

62. A method of administering a pharmaceutical agent to an organism having intestinal epithelium, said method comprising contacting said intestinal epithelium with a purified synthetic polypeptide ligand comprising a 12-mer L-peptide or homologue thereof, said 12-mer L-peptide selected from the group consisting of SEQ ID NO:25 and SEQ ID NOs:38-39 wherein said homologue is at least 9/12 homologous to a 12-mer peptide selected from said group and wherein said 12-mer L-peptide or homologue thereof, when integrated as an N-terminal PIII fusion peptide of an M13 phage confers an ability to bind the phage to either Caco-2 cell, IEC-6 cell, rat, mouse, pig or dog homogenate membrane fractions, said ability being at least as great as that conferred by a similarly integrated 12-mer peptide of SEQ ID NO:67, said ligand being covalently, or non-covalently bound to, a carrier entity, wherein said purified synthetic polypeptide ligand is a peptide integrated into the protein of a phage which is coated, adsorbed-or covalently bonded to a surface of a carrier that is either a nanoparticle or microparticle.

63. The method of claim 62 , wherein said phage is modified to contain DNA encoding an antigen.

64. The method of claim 62 , wherein said nanoparticle or microparticle is loaded with a pharmaceutical agent or encapsulated with a pharmaceutical agent.

65. A method of administering a pharmaceutical agent to an organism having intestinal epithelium, said method comprising contacting said intestinal epithelium with a purified synthetic polypeptide ligand comprising a 12-mer L-peptide or homologue thereof, said 12-mer L-peptide selected from the group consisting of SEQ ID NO:25 and SEQ ID NOs:38-39 wherein said homologue is at least 9/12 homologous to a 12-mer peptide selected from said group and wherein said 12-mer L-peptide or homologue thereof, when integrated as an N-terminal PIII fusion peptide of an M13 phage confers an ability to bind the phage to either Caco-2 cell, IEC-6 cell, rat, mouse, pig or dog homogenate membrane fractions, said ability being at least as great as that conferred by a similarly integrated 12-mer peptide of SEQ ID NO:67, said ligand being covalently, or non-covalently bound to, a carrier entity, wherein the purified synthetic polypeptide ligand comprises a zinc-binding motif, and said ligand is contacted with said epithelium in the presence of zinc.