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

1. A purified synthetic polypeptide ligand comprising a 12-mer L-peptide or a homologue thereof, said 12-mer L-peptide consisting of SEQ ID NO:1 wherein said homologue is at least {fraction (10/12)} homologous to said 12-mer peptide 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 to bind being at least as great as that conferred by a similarly integrated 12-mer peptide of SEQ ID NO:67.

2. A purified synthetic polypeptide ligand of claim 1 , wherein said ligand comprises a zinc-binding domain.

3. A purified synthetic polypeptide ligand of claim 1 , wherein the homologue is at least {fraction (11/12)} homologous to a 12-mer peptide.

4. A purified synthetic polypeptide ligand of claim 1 , wherein said ligand comprises a 12-mer L-peptide consisting of SEQ ID NO:1.

5. A purified synthetic polypeptide ligand of claim 1 , wherein said ligand consists of an amino acid sequence consisting of SEQ ID NO:1 or homologue thereof.

6. A purified synthetic polypeptide ligand of claim 1 , wherein said ligand consists of a 12-mer L-peptide consisting of SEQ ID NO:1.

7. A purified synthetic polypeptide ligand of claim 1 , wherein said ligand is at most 200 amino acids in length.

8. A purified synthetic polypeptide ligand of claim 1 , wherein said polypeptide ligand is at least 30 amino acids in length.

9. A purified synthetic polypeptide ligand comprising a 12-mer D-peptide or a homologue thereof, said 12-mer D-peptide being the D-form of a 12-mer L-peptide consisting of SEQ ID NO:1, wherein said homologue is at least {fraction (9/12)} homologous to said 12-mer D-peptide and wherein said 12-mer D-peptide 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 to bind being at least as great as that conferred by a similarly integrated 12-mer peptide of SEQ ID NO:67.

10. A purified synthetic polypeptide ligand of claim 9 , wherein said ligand comprises a zinc-binding domain.

11. A purified synthetic polypeptide ligand of claim 9 , wherein the homologue is at least {fraction (10/12)} homologous to a 12-mer D-peptide.

12. A purified synthetic polypeptide ligand of claim 9 , wherein the homologue is at least {fraction (11/12)} homologous to a 12-mer D-peptide.

13. A purified synthetic polypeptide ligand of claim 9 , wherein said ligand comprises a 12-mer D-peptide being the D-form of a 12-mer consisting of SEQ ID NO:1.

14. The purified synthetic polypeptide ligand of claim 9 , wherein said ligand consists of the D-form of a 12-mer L-peptide consisting of SEQ ID NO:1.

15. A purified synthetic polypeptide ligand of claim 9 , wherein said ligand is at most 200 amino acids in length.

16. A purified synthetic polypeptide ligand of claim 9 , wherein said polypeptide ligand is at least 30 amino acids in length.

17. A purified synthetic polypeptide ligand comprising a 12-mer retro-inverted peptide or a homologue thereof, said 12-mer retro-inverted peptide being the retro-inverted form of a 12-mer L-peptide consisting of SEQ ID NO:1, wherein said homologue is at least {fraction (9/12)} homologous to said 12-mer retro-inverted 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 to bind being at least as great as that conferred by a similarly integrated 12-mer peptide of SEQ ID NO:67.

18. A purified synthetic polypeptide ligand of claim 17 , wherein said ligand comprises a zinc-binding domain.

19. A purified synthetic polypeptide ligand of claim 17 , wherein the homologue is at least {fraction (10/12)} homologous to a 12-mer retro-inverted peptide.

20. A purified synthetic polypeptide ligand of claim 17 , wherein the homologue is at least {fraction (11/12)} homologous to a 12-mer retro-inverted peptide.

21. A purified synthetic polypeptide ligand of claim 17 , wherein said ligand comprises a 12-mer retro-inverted peptide being the retro-inverted form of a 12-mer L-peptide consisting of SEQ ID NO:1.

22. A purified synthetic polypeptide ligand of claim 17 , wherein said ligand consists of an amino acid sequence selected from the group consisting of the retro-inverted form of a 12-mer L-peptide of SEQ ID NO:1 or a homologue thereof.

23. A purified synthetic polypeptide ligand of claim 17 , wherein said ligand consists of the retro-inverted form of a 12-mer L-peptide consisting of SEQ ID NO:1.

24. A purified synthetic polypeptide ligand of claim 17 , wherein said ligand is at most 200 amino acids in length.

25. The purified synthetic polypeptide ligand of claim 17 , wherein said polypeptide ligand is at least 30 amino acids in length.

26. A purified synthetic polypeptide ligand of claim 1 , 9 , or 17 , wherein said polypeptide ligand is integrated into the protein of a phage.

27. The ligand of claim 26 , 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.

28. The ligand of claim 26 , 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.

29. A purified synthetic polypeptide ligand of claim 1 , 9 , or 17 , wherein said polypeptide ligand is covalently or non-covalently bound to a carrier entity comprising a pharmaceutical agent.

30. The purified synthetic polypeptide ligand of claim 29 , wherein said carrier entity is selected from the group consisting of a nanoparticle, a microparticle, a liposome, a bacterium, a phage and a virus.

31. The purified synthetic polypeptide ligand of claim 30 , wherein said carrier entity is selected from the group consisting of a nanoparticle, microparticle and a liposome.

32. The purified synthetic polypeptide ligand of claim 31 , wherein said carrier entity has a largest dimension that is in the range of 10 nm to 500 μm.

33. The ligand of claim 29 , wherein said pharmaceutical agent is a drug or therapeutic agent.

34. The ligand of claim 29 , wherein said pharmaceutical agent is a pathogen antigen.

35. The ligand of claim 29 , wherein said pharmaceutical agent is an adjuvant.

36. The purified synthetic polypeptide ligand of claim 29 , wherein said carrier entity is selected from the group consisting of a phage and a virus.

37. 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, said ligand being covalently, or non-covalently bound to, a carrier entity, wherein said ligand is selected from the group consisting of:

(a) a ligand comprising a 12-mer L-peptide, fragment or a homologue thereof, said 12-mer L-peptide consisting of SEQ ID NO:1 wherein said fragment is at least five contiguous amino acids and wherein said homologue is at least {fraction (9/12)} homologous to said 12-mer peptide and wherein said 12-mer L-peptide, fragment 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 to bind being at least as great as that conferred by a similarly integrated 12-mer peptide of SEQ ID NO:67;

(b) a ligand comprising a 12-mer D-peptide, fragment or a homologue thereof, said 12-mer D-peptide being the D-form of a 12-mer L-peptide consisting of SEQ ID NO:1, wherein said fragment is at least five contiguous amino acids and wherein said homologue is at least {fraction (9/12)} homologous to said 12-mer D-peptide and wherein said 12-mer D-peptide, fragment 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 to bind being at least as great as that conferred by a similarly integrated 12-mer peptide of SEQ ID NO:67; and

(c) a ligand comprising a 12-mer retro-inverted peptide, fragment or a homologue thereof, said 12-mer retro-inverted peptide being the retro-inverted form of a 12-mer L-peptide consisting of SEQ ID NO:1, wherein said fragment is at least five contiguous amino acids and wherein said homologue is at least {fraction (9/12)} homologous to said 12-mer retro-inverted peptide arid wherein said 12-mer retro-inverted peptide, fragment 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 to bind being at least as great as that conferred by a similarly integrated 12-mer peptide of SEQ ID NO:67.

38. The method of claim 37 , wherein said organism is a mammal.

39. The method of claim 38 , wherein said mammal is a human.

40. The method of claim 37 , wherein said carrier entity is selected from the group consisting of a nanoparticle, microparticle, liposome, bacterium, phage and a viral carrier.

41. The method of claim 37 , wherein said carrier entity is selected from the group consisting of a nanoparticle, microparticle and liposome.

42. The method of claim 41 , wherein said carrier entity has its major dimension in the range of 10 nm to 500 μm.

43. The method of claim 41 , wherein said nanoparticle, microparticle, or liposome is loaded with a pharmaceutical agent or encapsulated with a pharmaceutical agent.

44. The method of claim 37 , wherein said administration is done via the oral route.

45. The method of claim 37 , wherein said administration is done via either a rectal, subcutaneous, intramuscular, nasal or intravenous route.

46. The method of claim 37 , wherein said pharmaceutical agent is a vaccine.

47. The method of claim 37 , 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.

48. The method of claim 47 , wherein said phage is modified to contain DNA encoding an antigen.

49. The method of claim 47 , wherein said nanoparticle or microparticle is loaded with a pharmaceutical agent or encapsulated with a pharmaceutical agent.

50. A method of claim 37 , wherein the purified synthetic polypeptide ligand comprises a zinc-binding motif , and said ligand is contacted with said epithelium in the presence of zinc.

51. A method of claim 37 , wherein said carrier entity is selected from the group consisting of a phage and a viral carrier.

52. The method of claim 51 , wherein said phage comprises a targeting ligand on its surface.

53. A purified synthetic polypeptide ligand comprising a fragment selected from the group consisting of

(a) a fragment of a 12-mer L-peptide consisting of SEQ ID NO:1 wherein said fragment is at least eight contiguous amino acids and wherein said fragment, 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 to bind being at least as great as that conferred by a similarly integrated 12-mer peptide of SEQ ID NO:67;

(b) a fragment of a 12-mer D-peptide, said 12-mer D-peptide being the D-form of a 12-mer L-peptide consisting of SEQ ID NO:1, wherein said fragment is at least eight contiguous amino acids and wherein said fragment, 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 to bind being at least as great as that conferred by a similarly integrated 12-mer peptide of SEQ ID NO:67; and

(c) a fragment of a 12-mer retro-inverted peptide, said 12-mer retro-inverted peptide being the retro-inverted form of a 12-mer L-peptide consisting of SEQ ID NO:1, wherein said fragment is at least eight contiguous amino acids and wherein said fragment, 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 to bind being at least as great as that conferred by a similarly integrated 12-mer peptide of SEQ ID NO:67.

54. A purified synthetic polypeptide ligand of claim 53 , wherein said ligand comprises a zinc-binding domain.

55. A purified synthetic polypeptide ligand of claim 53 , wherein said ligand consists of a fragment of a 12-mer L-peptide consisting of SEQ ID NO:1.

56. A purified synthetic polypeptide ligand of claim 53 , wherein said ligand is at most 200 amino acids in length.

57. A purified synthetic polypeptide ligand of claim 53 , wherein said ligand is at least 12 amino acids in length.

58. A purified synthetic polypeptide ligand of claim 53 , wherein said polypeptide ligand is at least 30 amino acids in length.