Claims
- 1. An isolated MMP-2 selective substrate polypeptide, comprising an amino acid sequence selected from the group consisting of: SEQ ID NOS:1-27, or a functional peptidomimetic thereof.
- 2. The isolated MMP-2 selective substrate polypeptide of claim 1, wherein said polypeptide has less than about 100 amino acids.
- 3. The isolated MMP-2 selective substrate polypeptide of claim 1, wherein said polypeptide has less than about 20 amino acids.
- 4. The isolated MMP-2 selective substrate polypeptide of claim 1, wherein said polypeptide, or functional peptidomimetic thereof, is linked to a moiety.
- 5. The isolated MMP-2 selective substrate polypeptide of claim 4, wherein said moiety is a diagnostic agent.
- 6. The isolated MMP-2 selective substrate polypeptide of claim 5, wherein said diagnostic agent is a quenched fluorophore.
- 7. The isolated MMP-2 selective substrate polypeptide of claim 4, wherein said moiety is a therapeutic moiety.
- 8. The isolated MMP-2 selective substrate polypeptide of claim 7, wherein said therapeutic moiety is a chemotherapeutic agent.
- 9. The isolated MMP-2 selective substrate polypeptide of claim 7, wherein said therapeutic moiety is selected from the group consisting of an anti-angiogenic agent, a pro-angiogenic agent and an agent that promotes tissue repair.
- 10. A method of preferentially directing a moiety to a site of MMP-2 activity, comprising administering to a subject an effective amount of an isolated MMP-2 selective substrate polypeptide linked to said moiety, wherein said polypeptide comprises an amino acid sequence selected from the group consisting of: (I/L)-X-X-XHy-(T/L/I/Y)-X (SEQ ID NO:45), X-S-X-XHy-(T/L/K)-X (SEQ ID NO:46), and H-X-X-XHy-X-(T/A) (SEQ ID NO:47) wherein XHy is the P1′ substituent of the substrate, or a functional peptidomimetic thereof.
- 11. The method of claim 10, wherein said isolated MMP-2 selective substrate polypeptide linked to said moiety comprises an amino acid sequence selected from the group consisting of: SEQ ID NOS:1-27, or a functional peptidomimetic thereof.
- 12. The method of claim 10, wherein said site of MMP-2 activity is angiogenic vasculature.
- 13. The method of claim 10, wherein said isolated MMP-2 selective substrate polypeptide has less than about 100 amino acids.
- 14. The method of claim 10, wherein said isolated MMP-2 selective substrate polypeptide has less than about 20 amino acids.
- 15. The method of claim 10, wherein said moiety is a diagnostic agent.
- 16. The method of claim 15, wherein said diagnostic agent is a quenched fluorophore.
- 17. The method of claim 10, wherein said moiety is a therapeutic moiety.
- 18. The method of claim 17, wherein said therapeutic moiety is a chemotherapeutic agent.
- 19. The method of claim 17, wherein said therapeutic moiety is selected from the group consisting of an anti-angiogenic agent, pro-angiogenic agent and an agent that promotes tissue repair.
- 20. An isolated MMP-9 selective substrate polypeptide, comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:28-35, or a functional peptidomimetic thereof.
- 21. The isolated MMP-9 selective substrate polypeptide of claim 20, wherein said polypeptide has less than about 100 amino acids.
- 22. The isolated MMP-9 selective substrate polypeptide of claim 20, wherein said polypeptide has less than about 20 amino acids.
- 23. The isolated MMP-9 selective substrate polypeptide of claim 20, wherein said polypeptide, or functional peptidomimetic thereof, is linked to a moiety.
- 24. The isolated MMP-9 selective substrate polypeptide of claim 23, wherein said moiety is a diagnostic agent.
- 25. The isolated MMP-9 selective substrate polypeptide of claim 24, wherein said diagnostic agent is a quenched fluorophore.
- 26. The isolated MMP-9 selective substrate polypeptide of claim 23, wherein said moiety is a therapeutic moiety.
- 27. The isolated MMP-9 selective substrate polypeptide of claim 26, wherein said therapeutic moiety is a chemotherapeutic agent.
- 28. The isolated MMP-9 selective substrate polypeptide of claim 26, wherein said therapeutic moiety is selected from the group consisting of an anti-angiogenic agent, a pro-angiogenic agent and an agent that promotes tissue repair.
- 29. A method of preferentially directing a moiety to a site of MMP-9 activity, comprising administering to a subject an effective amount of an isolated MMP-9 selective substrate polypeptide linked to said moiety, wherein said polypeptide comprises an amino acid sequence of P-R-X-XHy-(S/T) (SEQ ID NO:44), where XHy is the P1′ substituent of the substrate, or a functional peptidomimetic thereof.
- 30. The method of claim 29, wherein said isolated MMP-9 selective substrate polypeptide linked to said moiety comprises an amino acid sequence selected from the group consisting of: SEQ ID NOS:28-35.
- 31. The method of claim 29, wherein said site of MMP-9 activity is angiogenic vasculature.
- 32. The method of claim 29, wherein said isolated MMP-9 selective substrate polypeptide has less than about 100 amino acids.
- 33. The method of claim 29, wherein said isolated MMP-9 selective substrate polypeptide has less than about 20 amino acids.
- 34. The method of claim 29, wherein said moiety is a diagnostic agent.
- 35. The method of claim 34, wherein said diagnostic agent is a quenched fluorophore.
- 36. The method of claim 29, wherein said moiety is a therapeutic moiety.
- 37. The method of claim 36, wherein said therapeutic moiety is a chemotherapeutic agent.
- 38. The method of claim 36, wherein said therapeutic moiety is selected from the group consisting of an anti-angiogenic agent, pro-angiogenic agent and an agent that promotes tissue repair.
- 39. An isolated MT1-MMP selective substrate polypeptide, comprising an amino acid sequence of SEQ ID NOS:36-40, or a functional peptidomimetic thereof.
- 40. The isolated MT1-MMP selective substrate polypeptide of claim 39, wherein said polypeptide has less than about 100 amino acids.
- 41. The isolated MT1-MMP selective substrate polypeptide of claim 39, wherein said polypeptide has less than about 20 amino acids.
- 42. The isolated MT1-MMP selective substrate polypeptide of claim 39, wherein said polypeptide, or functional peptidomimetic thereof, is linked to a moiety.
- 43. The isolated MT1-MMP selective substrate polypeptide of claim 42, wherein said moiety is a diagnostic agent.
- 44. The isolated MT1-MMP selective substrate polypeptide of claim 43, wherein said diagnostic agent is a quenched fluorophore.
- 45. The isolated MT1-MMP selective substrate polypeptide of claim 42, wherein said moiety is a therapeutic moiety.
- 46. The isolated MT1-MMP selective substrate polypeptide of claim 45, wherein said therapeutic moiety is a chemotherapeutic agent.
- 47. The isolated MT1-MMP selective substrate polypeptide of claim 45, wherein said therapeutic moiety is selected from the group consisting of an anti-angiogenic agent, a pro-angiogenic agent and an agent that promotes tissue repair.
- 48. A method of preferentially directing a moiety to a site of MT1-MMP activity, comprising administering to a subject an effective amount of an isolated MT1-MMP selective substrate polypeptide linked to said moiety, wherein said polypeptide comprises an amino acid sequence selected from the group consisting of: SEQ ID NOS:36-40, or a functional peptidomimetic thereof.
- 49. The method of claim 48, wherein said site of MT1-MMP activity is angiogenic vasculature.
- 50. The method of claim 48, wherein said isolated MT1-MMP selective substrate polypeptide has less than about 100 amino acids.
- 51. The method of claim 48, wherein said isolated MT1-MMP selective substrate polypeptide has less than about 20 amino acids.
- 52. The method of claim 48, wherein said moiety is a diagnostic agent.
- 53. The method of claim 52, wherein said diagnostic agent is a quenched fluorophore.
- 54. The method of claim 48, wherein said moiety is a therapeutic moiety.
- 55. The method of claim 54, wherein said therapeutic moiety is a chemotherapeutic agent.
- 56. The method of claim 54, wherein said therapeutic moiety is selected from the group consisting of an anti-angiogenic agent, pro-angiogenic agent and an agent that promotes tissue repair.
Parent Case Info
[0001] This application is based on, and claims the benefit of, U.S. Provisional Application No. ______ (yet to be assigned), filed Sep. 14, 2001, which was converted from U.S. Ser. No. 09/953,592, and which is incorporated herein by reference.
Government Interests
[0002] This invention was made with government support under grant numbers CA 69036 and AR 42750 awarded by the National Institutes of Health. The United States Government has certain rights in this invention.