Claims
- 1. A cyclic peptide having the formula:
- 2. A cyclic peptide according to claim 1, the peptide has an N-terminal acetyl, formyl or mesyl group.
- 3. A cyclic peptide according to claim 1, wherein X and Y are each independently selected from the group consisting of cysteine, penicillamine, β,β-tetramethylene cysteine, β,β-pentamethylene cysteine, β-mercaptopropionic acid, β,β-pentamethylene-β-mercaptopropionic acid, 2-mercaptobenzene, 2-mercaptoaniline and 2-mercaptoproline.
- 4. A cyclic peptide according to claim 1, wherein X and Y are cysteine residues.
- 5. A cyclic peptide according to claim 1, wherein the cyclic peptide comprises a sequence selected from the group consisting of: CHAVCS (SEQ ID NO:87), CHAVCSS (SEQ ID NO:89), SCHAVCS (SEQ ID NO:90), CHAVCY (SEQ ID NO:85), YCHAVC (SEQ ID NO:10), CHAVCT (SEQ ID NO:91), CHAVCD (SEQ ID NO:93) and CHAVCE (SEQ ID NO:92).
- 6. A cyclic peptide according to claim 5, wherein the cyclic peptide has an N-terminal acetyl group or CH3—SO2— group, and a C-terminal amide group.
- 7. A cyclic peptide selected from the group consisting of N-Ac-CHAVYC-NH2 (SEQ ID NO:94), N-Ac-CHAVPC-NH2 (SEQ ID NO:99), N-Ac-CFSHAVC-NH2 (SEQ ID NO:85), N-Ac-CLFSHAVC-NH2 (SEQ ID NO:86), CH3-SO2-HN-CHAVC-NH2 (SEQ ID NO:96), HC(O)-NH-CHAVC-NH2 (SEQ ID NO:96), N-Ac-CHAVPen-NH2 (SEQ ID NO:97) and N-Ac-PenHAVC-NH2 (SEQ ID NO:98).
- 8. A cell adhesion modulating agent comprising a cyclic peptide according to any one of claims 1-7.
- 9. A cell adhesion modulating agent according to claim 8 linked to a targeting agent.
- 10. A cell adhesion modulating agent according to claim 8 linked to a drug.
- 11. A cell adhesion modulating agent according to claim 8 linked to a solid support.
- 12. A cell adhesion modulating agent according to claim 11, wherein the solid support is a polymeric matrix.
- 13. A cell adhesion modulating agent according to claim 11, wherein the solid support is selected from the group consisting of plastic dishes, plastic tubes, sutures, membranes, ultra thin films, bioreactors and microparticles.
- 14. A cell adhesion modulating agent according to claim 13, further comprising one or more of:
(a) a cell adhesion recognition sequence that is bound by an adhesion molecule other than a cadherin, wherein the cell adhesion recognition sequence is separated from any HAV sequence(s) by a linker; and/or (b) an antibody or antigen-binding fragment thereof that specifically binds to a cell adhesion recognition sequence bound by an adhesion molecule other than a cadherin.
- 15. A cell adhesion modulating agent according to claim 14, wherein the adhesion molecule is selected from the group consisting of integrins, occludin, N-CAM, desmogleins, desmocollins, fibronectin, laminin and other extracellular matrix proteins.
- 16. A cell adhesion modulating agent according to claim 8 linked to a detectable marker.
- 17. A pharmaceutical composition comprising a cell adhesion modulating agent according to claim 8, in combination with a pharmaceutically acceptable carrier.
- 18. A composition according to claim 17, further comprising a drug.
- 19. A composition according to claim 17, wherein the cell adhesion modulating agent is present within a sustained-release formulation.
- 20. A pharmaceutical composition according to claim 17, further comprising one or more of:
(a) a peptide comprising a cell adhesion recognition sequence that is bound by an adhesion molecule other than a cadherin; and/or (b) an antibody or antigen-binding fragment thereof that specifically binds to a cell adhesion recognition sequence bound by an adhesion molecule other than a cadherin.
- 21. A pharmaceutical composition according to claim 20, wherein the adhesion molecule is selected from the group consisting of integrins, occludin, N-CAM, desmogleins, desmocollins, fibronectin, laminin and other extracellular matrix proteins.
- 22. A method for inhibiting the development of a cancer in a mammal, comprising administering to a mammal a cell adhesion modulating agent according to claim 8, and thereby inhibiting the development of a cancer in the mammal.
- 23. A method according to claim 22, wherein the cancer is selected from the group consisting of carcinomas, leukemias and melanomas.
- 24. A method according to claim 22, wherein the modulating agent has the formula:
- 25. A method according to claim 24, wherein the peptide has an N-terminal acetyl, formyl or mesyl group.
- 26. A method according to claim 24, wherein X and Y are cysteine residues.
- 27. A method according to claim 24, wherein the cyclic peptide comprises a sequence selected from the group consisting of: CHAVCS (SEQ ID NO:87), CHAVCSS (SEQ ID NO:89), SCHAVCS (SEQ ID NO:90), CHAVCY (SEQ ID NO:85), YCHAVC (SEQ ID NO: 10), CHAVCT (SEQ ID NO:91), CHAVCD (SEQ ID NO:93) and CHAVCE (SEQ ID NO:92).
- 28. A method according to claim 27, wherein the cyclic peptide has an N-terminal acetyl group or CH3—SO2— group, and a C-terminal amide group.
- 29. A method according to claim 22, wherein the modulating agent comprises a cyclic peptide selected from the group consisting of N-Ac-CHAVYC-NH2 (SEQ ID NO:94), N-Ac-CHAVPC-NH2 (SEQ ID NO:99), N-Ac-CFSHAVC-NH2 (SEQ ID NO: 85), N-Ac-CLFSHAVC-NH2 (SEQ ID NO:86), CH3-SO2-HN-CHAVC-NH2 (SEQ ID NO:96), HC(O)-NH-CHAVC-NH2 (SEQ ID NO:96), N-Ac-CHAVPen-NH2 (SEQ ID NO:97) and N-Ac-PenHAVC-NH2 (SEQ ID NO:98).
- 30. A method according to claim 22, wherein the modulating agent is linked to a targeting agent.
- 31. A method according to claim 22, wherein the modulating agent further comprises one or more of:
(a) a cell adhesion recognition sequence bound by an adhesion molecule other than a classical cadherin, wherein the cell adhesion recognition sequence is separated from any HAV sequence(s) by a linker; and/or (b) an antibody or antigen-binding fragment thereof that binds to a cell adhesion recognition sequence bound by an adhesion molecule other than a classical cadherin.
- 32. A method according to claim 31, wherein the cell adhesion recognition sequence comprises a sequence selected from the group consisting of NQK, NRN, NKD, EKD, ERD, DDK, EEY, EAQ, IYSY (SEQ ID NO:58), TSSY (SEQ ID NO:59), VTAF (SEQ ID NO:60), VSAF (SEQ ID NO:61), RGD and LYHY (SEQ ID NO:55).
- 33. A method according to claim 22, wherein the modulating agent is present within a pharmaceutical composition comprising a pharmaceutically acceptable carrier.
- 34. A method according to claim 33, wherein the pharmaceutical composition further comprises a modulator of cell adhesion comprising one or more of:
(a) a cell adhesion recognition sequence bound by an adhesion molecule other than a classical cadherin; and/or (b) an antibody or antigen-binding fragment thereof that binds to a cell adhesion recognition sequence bound by an adhesion molecule other than a classical cadherin.
- 35. A method according to claim 34, wherein the cell adhesion recognition sequence comprises a sequence selected from the group consisting of NQK, NRN, NKD, EKD, ERD, DDK, EEY, EAQ, IYSY (SEQ ID NO:58), TSSY (SEQ ID NO:59), VTAF (SEQ ID NO:60), VSAF (SEQ ID NO:61), RGD and LYHY (SEQ ID NO:55).
- 36. A method for stimulating blood vessel regression, comprising administering to a mammal a cell adhesion modulating agent comprising the sequence His-Ala-Val within a cyclic peptide ring, wherein the cyclic peptide modulates cadherin-mediated cell adhesion, and thereby stimulating blood vessel regression in the mammal.
- 37. A method according to claim 36, wherein a modulating agent according to claim 8 is administered to the mammal.
- 38. A method according to claim 36, wherein the mammal is afflicted with cancer, psoriasis, arthritis or age-related macular degeneration.
- 39. A method according to claim 36, wherein the modulating agent has the formula:
- 40. A method according to claim 39, wherein X has an N-terminal acetyl, formyl or mesyl group.
- 41. A method according to claim 39, wherein X and Y are cysteine residues.
- 42. A method according to claim 39, wherein the cyclic peptide comprises a sequence selected from the group consisting of: CHAVCS (SEQ ID NO:87), CHAVCSS (SEQ ID NO:89), SCHAVCS (SEQ ID NO:90), CHAVCY (SEQ ID NO:85), YCHAVC (SEQ ID NO:10), CHAVCT (SEQ ID NO:91), CHAVCD (SEQ ID NO:93) and CHAVCE (SEQ ID NO:92).
- 43. A method according to claim 42, wherein the cyclic peptide has an N-terminal acetyl group or CH3—SO2— group, and a C-terminal amide group.
- 44. A method according to claim 37, wherein the modulating agent comprises a cyclic peptide selected from the group consisting of N-Ac-CHAVYC-NH2 (SEQ ID NO:94), N-Ac-CHAVPC-NH2 (SEQ ID NO:99), N-Ac-CFSHAVC-NH2 (SEQ ID NO:85), N-Ac-CLFSHAVC-NH2 (SEQ ID NO:86), CH3-SO2-HN-CHAVC-NH2 (SEQ ID NO:96), HC(O)-NH-CHAVC-NH2 (SEQ ID NO:96), N-Ac-CHAVPen-NH2 (SEQ ID NO:97) and N-Ac-PenHAVC-NH2 (SEQ ID NO:98).
- 45. A method according to claim 36, wherein the modulating agent is linked to a targeting agent.
- 46. A method according to claim 36, wherein the modulating agent further comprises one or more of:
(a) a cell adhesion recognition sequence bound by an adhesion molecule other than a classical cadherin, wherein the cell adhesion recognition sequence is separated from any HAV sequence(s) by a linker; and/or (b) an antibody or antigen-binding fragment thereof that binds to a cell adhesion recognition sequence bound by an adhesion molecule other than a classical cadherin.
- 47. A method according to claim 46, wherein the cell adhesion recognition sequence comprises a sequence selected from the group consisting of NQK, NRN, NKD, EKD, ERD, DDK, EEY, EAQ, IYSY (SEQ ID NO:58), TSSY (SEQ ID NO:59), VTAF (SEQ ID NO:60), VSAF (SEQ ID NO:61), RGD and LYHY (SEQ ID NO:55).
- 48. A method according to claim 36, wherein the modulating agent is present within a pharmaceutical composition comprising a pharmaceutically acceptable carrier.
- 49. A method according to claim 48, wherein the pharmaceutical composition further comprises a modulator of cell adhesion comprising one or more of:
(a) a cell adhesion recognition sequence bound by an adhesion molecule other than a classical cadherin; and/or (b) an antibody or antigen-binding fragment thereof that binds to a cell adhesion recognition sequence bound by an adhesion molecule other than a classical cadherin.
- 50. A method according to claim 49, wherein the cell adhesion recognition sequence comprises a sequence selected from the group consisting of NQK, NRN, NKD, EKD, ERD, DDK, EEY, EAQ, IYSY (SEQ ID NO:58), TSSY (SEQ ID NO:59), VTAF (SEQ ID NO:60), VSAF (SEQ ID NO:61), RGD and LYHY (SEQ ID NO:55).
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. Ser. No. 09/357,717, filed Jul. 20, 1999, which is a continuation-in-part of U.S. Ser. No. 09/248,074, filed Feb. 10, 1999, which is a continuation-in-part of U.S. Ser. No. 08/996,679, filed Dec. 23, 1997, which is a continuation in part of U.S. Ser. No. 08/893,534, filed Jul. 11, 1997, which claims the benefit of U.S. Provisional Application No. 60/021,612, filed on Jul. 12, 1996.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60021612 |
Jul 1996 |
US |
Divisions (1)
|
Number |
Date |
Country |
Parent |
09458870 |
Dec 1999 |
US |
Child |
10105008 |
Mar 2002 |
US |
Continuation in Parts (4)
|
Number |
Date |
Country |
Parent |
09357717 |
Jul 1999 |
US |
Child |
09458870 |
Dec 1999 |
US |
Parent |
09248074 |
Feb 1999 |
US |
Child |
09357717 |
Jul 1999 |
US |
Parent |
08996679 |
Dec 1997 |
US |
Child |
09248074 |
Feb 1999 |
US |
Parent |
08893534 |
Jul 1997 |
US |
Child |
08996679 |
Dec 1997 |
US |